Abstract Book - Österreichische Gesellschaft für Allergologie und

Transcription

Abstract
Book
Austrian
Society for
Allergology and
Immunology
ÖGAI Annual Meeting
Salzburg
Nov. 6 - 8, 2014
Sponsors & Exhibitor Map
Welcome & Committee
General Information Programme at a glance
Programm: Klinischer Allergietag
Invited Speakers/ Vortragende
Exhibitors
Abstracts: Titles and Authors
Abstracts: Keynote Lectures
Abstracts: Klinischer Allergietag
Abstracts: Oral and Poster Sessions
Große Universitätsaula
am Max Reinhardt Platz
im Festspielbezirk
2
3
4
5-6
7
8-9
10 - 11
12 - 15
16 - 23
24 - 29
30-146
2014
Austrian Society for Allergology and Immunology
Jahrestagung 2014, Salzburg, November 6-8, 2014
Partners and Exhibitors
Partners
and
Exhibitors
FWF SFB F46: Towards prevention & therapy of allergy
(Coordinator: Prof. Rudolf Valenta)
supporting
programmes
FWF PhD Program W1248: Molecular, Cellular and Clinical Allergology
(MCCA) (Coordinator: Prof. Winfried Pickl)
FWF PhD Program W1213: Immunity in Cancer and Allergy
(ICA)(Coordinator: Prof. Josef Thalhamer)
FWF PhD Program W1253: Host response in opportunistic infections
(HOROS) (Coordinator: Prof. Reinhard Würzner)
FWF PhD Program W1212: Inflammation and Immunity
(IAI) (Coordinator: Prof. Maria Sibilia)
Universität Salzburg Schwerpunkt Biowissenschaften und Gesundheit
(Coordinator: Prof. Josef Thalhamer)
Shire
ÖGAI Jahrestagung 2014
Universität, Foyer 1. Obergeschoß
Aussteller Standplan
Miltenyi
Biotec GmbH
Exhibitors
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MaxReinhardtPlatz
Welcome and Committee
Welcome
Dear friends and colleagues,
On behalf of the Local Organising Committee and the Austrian Society for Allergology and
Immunology (ÖGAI) I would like to warmly welcome you to Salzburg for the ÖGAI 2014 Annual
Meeting. The congress venue, the Große Aula, is one of the most beautiful and prestigious rooms of
the University of Salzburg. This is where Wolfgang Amadeus Mozart’s opera Apollo et Hyacinthus (K.
38), composed at the age of eleven, was given its first performance on 13 May 1767.
The meeting’s scientific program covers basic and clinical immunology, infectious diseases, immune
therapies, as well as basic and clinical allergology. These topics will be addressed by outstanding
keynote speakers during plenary lectures and by young scientists, who will have the opportunity
to present and discuss their work in oral and poster presentation sessions. I would like to give a
special thanks to all the speakers for their participation and willingness to share their knowledge,
results, and ideas. I extend my thanks to all the sponsors and exhibitors for their invaluable
contribution and support for the meeting.
I hope this meeting will provide you with a stimulating, enjoyable and inspiring experience in a
magical place filled with the sounds of beautiful music.
Fatima Ferreira
for the organizing committee
Organizing Committee
Fatima FERREIRA-BRIZA
(President)
Albert DUSCHL
Josef THALHAMER
Michael WALLNER
Richard WEISS
Jutta HOREJS-HÖCK
Gabriele GADERMAIER
Organizing Office
Karin MAYR-NESTELBACHER
DNA-CONSULT Sciencetainment
Torsten KLADE
Doris STAMPFER
Scientific Committee
Thomas HAWRANEK
Paracelsus Medizinische Privatuniversität Salzburg
Barbara BOHLE
Medizinische Universität Wien
Winfried PICKL
Medizinische Universität Wien
Stefan WÖHRL
Floridsdorfer Allergie Zentrum
Werner ABERER
Medizinische Universität Graz
Norbert REIDER
Medizinische Universität Innsbruck
Doris WILFLINGSEDER
Medizinische Universität Innsbruck
ÖGAI • Austrian Society for
Allergology and Immunology
Office: Veronika Maierhofer
Institut für Immunologie • Lazarettgasse 19
1090 Vienna • Austria • Tel.: 43(0)660/4977161
Fax: 431-40160-933201 • [email protected]
Publishing Info
Content:
Abstracts:
Design &
Organisation:
Print:
Committee
Contact
Publishing
Info
Organizing Committee / Organizing Office
The authors are responsible
for the content of the abstracts
Karin Mayr-Nestelbacher • DNA-CONSULT Sciencetainment
Huttegger Druck Salzburg
Liability is excluded for all printing errors and omissions
Seite 3
General Information
Registration
The registration desk will be located at the
entrance of the „Große Universitätsaula am MaxReinhardt-Platz im Festspielbezirk“ during the
following hours:
Thursday, Nov. 6th.
07:00 - 17:00
Friday, Nov. 7th. 08:00 - 17:00
Saturday, Nov. 8th 08.00 - 14:00
Contact Registration Desk
0043 676 7774565 • Nestelbacher
Opening hours • Meeting
Thursday, Nov. 6th.
Assembly and Prizes
Welcome Reception
07:00 - 17:00
17:00 - 18:30
18:30 - 20:00
Friday, Nov. 7th. 08:00 - 17:00
Saturday, Nov. 8th Farewell Gulasch
08.00 - 14:00
13:15 - 14:00
Opening hours • Exhibitors
Commercial exhibition will be on display in the
Foyer during the following hours:
Thursday, Nov. 6th.
11:00 - 17:00
Welcome Reception
18:30 - 20:00
Friday, Nov. 7th. 10:30 - 17:00
Saturday, Nov. 8th 08.00 - 11:30
Farewell Gulasch
13:15 - 14:00
Address
Große Universitätsaula
am Max-Reinhardt-Platz
im Festspielbezirk • 5020 Salzburg
Scientific Sessions
All talks will be held in the Aula of the congressvenue.
Oral Presentations
Please provide the data of your presentation at
the info desk until 9.00 am on the day of your
presentation.
Poster Presentations
The scientific posters will be presented in two
Poster Sessions on Thursday and on Friday. Posters
will be on display in the entrance foyer (ground
floor) and should be placed on the assigned board
on Thursday, Nov. 6th at 11:00 and removed
not before Friday, Nov. 7th after 17:00. Please
also note the schedule of poster sessions in the
programme. Pins will be provided. Your poster
number is printed in the list pages 12 - 15.
Digital Abstractbook
All abstracts of this Meeting are already available
as a free PDF-Download.
You find it at www.oegai.org
Meeting Attending Confirmation
If you need a confirmation please come to the
registration desk.
DFP Confirmation
You will get the confirmation for DFP points at the
registration desk.
Parking
Please use the Mönchsberggarage for parking.
For a reduction of the ticket price please bring the
ticket to the registration desk - it will be punched
there.
Registration fees
The registration fee for participants includes:
• admission to the annual meeting
and the exhibition
• digital meeting documentation
• daily coffee
• lunch on Thursday and Friday is not included; lunch for sale
• free WLAN
• Welcome Reception
• Farewell Gulasch on Saturday
Name badges
Our participants are asked to wear their name
badges all the time. The badge is essential for
admission to all scientific sessions, exhibits and it
is the entrance ticket to the welcome reception.
WLAN
Seite 4
WLAN is provided for free for participants and
exhibitors. Please fetch the login data at the
registration desk.
General Assembly
We cordially invite all ÖGAI members to the geral
assembly on Thursday, Nov. 6th at 17:00 in
the Aula.
Welcome Reception
We and the exhibitors invite you to the Welcome
Reception on Thursday, Nov. 6th at 18:30
in the Kahn-Foyer on the 1st floor of the
Universitätsaula.
Science Chat
Young scientists are invited for a „fireside chat“
with some of our international speakers. Scientists
will share with young investigators some of what
they have experienced and learned in their life in
science: Thursday, Nov. 6th. at 20:00
(duration: 1 hour) The meeting point will be
announced at the registration desk.
After the Science Chat we offer a
Pub Crawl
Join us and „investigate“ the „Salzburger BeislSzene“. Please ask for infos at the registration
desk.
Programme at a glance
Thursday: November 6th, 2014
07:00 - 08:55
08:55 - 09:00
09:00 - 09:30
Registration
Opening
Opening Keynote Lecture: Christian Münz (Switzerland) “Autophagy-mediated antigen presentation”
Invited by FWF PhD Program W1248: Molecular, Cellular and Clinical Allergology (MCCA) (Coordinator: Winfried F. Pickl)
09:30 - 11:00
09:30 - 10:00
Session 1
Keynote Lecture 1: Magnus Wickman (Sweden)
„Childhood-to-adolescence evolution of allergen-specific IgE antibodies“
Invited by FWF PhD Program W1213: Immunity in Cancer and Allergy (ICA) (Coordinator: Josef Thalhamer)
10:00- 11:00
Oral Presentations 1
Thomas EIWEGGER: Engineering hypoallergenic variants of the peanut allergens
Ara h 2 and Ara h 6
Heidi A. MÜLLER: The major cow milk allergen, Bos d 5, is able to bind siderophore
bound iron and influences T-helper cells according to its binding state
Teresa STEMESEDER: Why I? IgE profiling and lifestyle analysis of 501 Austrian school children
Eva WOLLMANN: Natural clinical tolerance to peanut in African patients is caused
by poor allergenic activity of peanut IgE
Victoria GARIB: Differences in molecular sensitization profiles towards animal allergens
revealed by allergen micro-array in two generation of patients with respiratory allergy
Christina BANNERT: Preventive sublingual immunotherapy in preschool children:
first evidence for safety and pro-tolerogenic effects
11:00 - 11:30
Coffee Break (sponsored by MEDA Pharma)
11:30 - 13:00
11:30 - 12:00
Session 2
Keynote Lecture 2: Teunis Geijtenbeek (The Netherlands) ”C-type lectins in infection and immunity”
Invited by FWF PhD Program W1253: “Host response in opportunistic
infections (HOROS)” (Coordinator: Reinhard Würzner)
12:00 - 13:00
Gerald WIRNSBERGER: Jagunal-homolog 1 is a critical regulator of neutrophil function in
fungal host defense
Daniela GALLERANO: Mapping of IgG, IgG-subclass, IgA and IgM reactivity profiles in African
and European HIV-infected individuals with an HIV-1 clade C proteome-based array
Leonhard X. HEINZ: Identification of a lipid-modifying enzyme as novel regulator of innate
immune responses
A. WAGNER: Age-related differences of humoral and cellular immune responses to primary
Japanese Encephalitis vaccination
Barbara KLEIN: The impact of an acute allergic inflammation on neurogenesis and microglia
in the hippocampal dentate gyrus
13:00 - 14:00
Lunch break
14:00 - 15:30
14:00 - 14:30
Session 3
Keynote Lecture 3: Jean Bousquet (France)
„MeDALL: Mechanisms of the Development of ALLergy“
Invited by FWF SFB F46: Towards prevention and therapy of allergy (Coordinator: Rudolf Valenta)
14:30 - 15:30
Claudia KITZMÜLLER: Innate responses and antigen-presenting capacity of oral epithelial cells
Barbara GEPP: Phosphorylation of CREB is upregulated in keratinocytes after treatment with
the major birch pollen allergen, Bet v 1, and birch pollen lipids
Raffaela CAMPANA: Epicutaneous application of recombinant Bet v 1 and Bet v 1 derivatives
induces allergen-specific IgG and T cell responses
Guido A. GUALDONI: Azithromycin inhibits IL-1 beta secretion of innate immune cells by
specificly inhibiting the NLRP3 inflammasome
Anastasia MESHCHERYAKOVA: Patient-specific immunological imprint within complex ovarian
cancer tissues
15:30 - 17:00
1st Poster Session with coffee (sponsored by MEDA Pharma)
Poster <34> to <82> Presentations 1.1 Allergenic Molecules and Epidemiology, 1.2 Infection and Immunity, 1.3 Development and Therapy of Allergies and other Immune Diseases
17:00
ÖGAI general assembly, awards ceremony
medals, prizes and welcome reception
Chair Opening:
Winfried Pickl
Vienna
Chairs Session 1:
Josef Thalhamer
Salzburg
Karin HoffmannSommergruber
Vienna
Chairs Session 2:
Reinhard
Würzner
Innsbruck
Doris
Wilflingseder
Innsbruck
Chairs Session 3:
Rudolf Valenta
Vienna
Gabriele
Gadermaier
Salzburg
Chairs Poster 1.1:
Magnus Wickman
Sweden
Eva UntersmayrElsenhuber, Vienna
Chairs Poster 1.2:
Hannes Stockinger
Vienna
Iris Gratz, Salzburg
Chairs Poster 1.3:
Sandra Scheiblhofer
Salzburg
Martin Himly
Salzburg
Programme at a glance
Chairs Session 4:
Patrizia Stoitzner
Innsbruck
Richard Weiss
Salzburg
Chairs Session 5:
Albert Duschl
Salzburg
Barbara Bohle
Vienna
Friday: November 7th, 2014
08:00 - 09:00
08:55 - 09:00
Registration
Opening
09:00 - 10:30
09:00 - 09:30
Session 4
Keynote Lecture 4: Claude-Agnès Reynaud (France)
“Diversity of human memory subsets”
Invited by FWF PhD Program W1213: Immunity in Cancer and Allergy (ICA) (Coordinator: Josef Thalhamer)
09:30 - 10:30
Yoan MACHADO: Carbohydrate coupling as a tool for modulation of the allergenicity and
immunological properties of the major birch pollen allergen Bet v 1.0101
Iris K. GRATZ: Controlling the balance between effector and regulatory T cells
in peripheral tissues
Mariana VÁZQUEZ-STRAUSS: Dual Role of NSAIDs: overcoming melanoma resistance
and enhancing cytotoxic potential of innate immune cells
Elisabeth GLITZNER: Specific roles for dendritic cell subsets during initiation and
progression of psoriasis
Daniela ORTNER: The role of Langerhans cells and natural killer cells in cancer
immune surveillance
10:30 - 11:00
Coffee Break (sponsored by Sony DADC)
11:00 - 12:30
11:00 - 11:30
Session 5
Keynote Lecture 5: Stephen Galli (USA)
„Testing the toxin hypothesis of allergy: Roles of mast cells and
IgE in innate and acquired resistance to venoms”
Invited by FWF SFB F46: Towards prevention and therapy of allergy (Coordinator: Rudolf Valenta)
11:30 - 12:30
Chairs Session 6:
Jutta HorejsHöck, Salzburg
Fatima Ferreira
Salzburg
Chairs Poster 2.1:
Fatima Ferreira
Salzburg
Dirk Strunk
Salzburg
Chairs Poster 2.2:
Stephen Galli
U.S.A.
Zsolt Szépfalusi
Vienna
Chairs Poster 2.3:
Claude-Agnès
Reynaud, France
Gerhard Zlabinger
Vienna
Chairs Closing:
Ursula Wiedermann-Schmidt
Vienna
Michael Wallner
Salzburg
Nazanin SAMADI: Characterization of the CD8+ T cell response to allergens
Martín R. CANDIA: Does signal one strength influence the phenotype and function of
human allergen-specific T lymphocytes?
Anna ONDRACEK: Nitrated Beta-Lactoglobulin enhances the anaphylactic response in a
murine food allergy model
Regina M. Selb: The trimeric complex of recombinant CD23 together with allergen
and allergen-specific IgE
Marion STEGER: Complement opsonization of A.fumigatus modifies dendritic cell
maturation and up-take
Kuan-Wei CHEN: Failure of specific immunotherapy (SIT) with house dust mite (HDM)
allergen extracts due to lack of HDM allergens capable of inducing specific
IgG responses in the therapeutic extracts
12:30 - 13:30
Lunch break
13:30 - 15:00
13:30 - 14:00
Session 6
Keynote Lecture 6: Alberto Mantovani (Italy)
“Molecular functions and regulation
circuits of inflammatory cytokines”
Invited by FWF PhD Program W1212: Inflammation and
Immunity (IAI) (Coordinator: Maria Sibilia)
14:00 - 15:00
Michaela MITTERMEIR: Signaling capacities of the IL-31 receptor complex
Madhura MODAK: Bidirectional polarization of T cell function via CD43
L. PANGRAZZI: Memory T cells and plasma cells niches in human bone marrow
Alexander ZWIRZITZ: The urokinase receptor as a positive regulator of T cell activation
Liisa ANDERSEN: Molecular analysis of MAZR function in CD4+ T cells
Julia MARSCHALLINGER: Structural and functional rejuvenation of the aged brain
by an approved anti-asthmatic drug
15:00 - 17:00
17:00 - 17:30
17:30 - 18:00
2nd Poster Session with coffee (sponsored by Sony DADC)
Poster <83> to <115> Presentations 2.1 Cellular Immunology,
2.2 Allergens and Effector Mechanisms, 2.3 Cytokines and Signal Transduction
Closing Keynote Lecture:
Maria Yazdanbakhsh (The Netherlands)
“Helminths and allergies: the IgE trick“
Invited by FWF PhD Program W1248: Molecular, Cellular and Clinical Allergology (MCCA) (Coordinator: Winfried F. Pickl)
Poster and oral presentations prize awards
Programmüberblick Klinischer Allergietag
Samstag, 8. November 2014
8:00 - 9:00
Registrierung
9:00 - 9:15
Begrüßung
9:15 - 9:50
„Nussknacker-Suite“:
Fälle aus dem allergologischen Alltag:
Univ. Doz. Dr. Wolfgang Hemmer
War es die Hirse? Und war es wirklich der Weizen?
- Zwei simple, aber doch lehrreiche rezente Fälle
Ass. Dr. med. Isabella Pohl
Frau mit Ausschlag
Doz. Dr. Stefan Wöhrl
Copaxone-Allergie in 1 ¾ Patienten
OA Dr. Thomas Hawranek
(Penicillin-Allergie – einmal anders)
9:50 - 10:25
Prof. Dr. med. Dr. phil. Johannes Ring (München)
Risiken der Allergiezunahme:
Was wir aus den Ost-West–Studien nach der
deutschen Wiedervereinigung gelernt haben.
10:25 - 11:00
Prof. Dr. med. Knut Brockow (München)
Analgetikaintoleranz: Braucht wirklich jeder Patient einen Provokationstest?
11:00 - 11:30
Kaffeepause (gesponsert von MEDA Pharma)
11:30 - 12:05
Prof. Dr. med. Margitta Worm (Berlin)
Volkskrankheit Anaphylaxie: Werden unsere Patienten ausreichend versorgt?
12:05 - 12:40
Privatdoz. Dr. med. Jörg Kleine-Tebbe (Berlin)
Wie evident ist die Rekombinanten-basierte Diagnostik in der Praxis?
12:40 - 13:15
Univ. Prof. Dr. med. Georg Stingl (Wien)
Biologika – ein modernes Allheilmittel?
„Farewell-Gulasch“ und Bier (gesponsert von Sony DADC)
Alle Sprecher des Klinischen Allergietages sind eingeladen vom
Schwerpunkt Biowissenschaften und Gesundheit
der Universität Salzburg (Koordinator: Josef Thalhamer)
Klinischer
Allergietag
in Deutsch
Vorsitzende:
Michael
Studnicka
Salzburg
Stefan Wöhrl
Wien
Vorsitzende:
Thomas
Hawranek
Salzburg
Petra
Zieglmayer
Wien
Seite 7
Invited Speakers
Jean Bousquet, born in 1946, is Full Professor of Pulmonary Medicine at
Montpellier University, France. For 13 years, he was the Director of the Inserm
(Institut de la Santé de et de la Recherche Médicale) laboratory “Immunopathology of Asthma”. He is Vice-President of the European Union-funded network
of excellence GA2LEN (Global Allergy and Asthma European Network). He was
granted as coordinator of the large scale Framework Programme 7 (EU) Integrated Project MeDALL (Mechanisms of the Development of Allergy). He has
chaired GINA (Global Initiative for Asthma), National Heart, Lung and Blood
Institute (NIH) and was the founder of ARIA (Allergic Rhinitis and its Impact
on Asthma), in collaboration with the World Health Organization (WHO). Jean
Bousquet was Chairman of the WHO Global Alliance against Chronic Respiratory Diseases (GARD 2005-2013). He has been the editor-in-chief of Allergy
(second ranking journal in the field, 2003-2009, IF: 6.2). His H factor is 90.
Stephen J. Galli is the chair of the Department of Pathology, the Mary Hewitt
Loveless, MD Professor, and a professor of pathology and of microbiology and
immunology at Stanford University School of Medicine, and, since 2009, the
Co-Director of the Stanford Center for Genomics and Personalized Medicine. His
research focuses on the development and function of mast cells and basophils
and the development of new animal models for studying the roles of these cells
in health and disease. Steve’s work has been recognized by Scientific Achievement Awards from the International Association of Allergy & Clinical Immunology (1997) and the World Allergy Organization (2011), the Rous-Whipple
Award of the American Society for Investigative Pathology (2014), and by his
election to various honorary societies, including the Collegium Internationale
Allergologicum, the Institute of Medicine of the US National Academies and the
Accademia Nazionale dei Lincei (National Academy of the Lynxes) in Rome.
Teunis B.H. Geijtenbeek is Professor of Cellular and Molecular Immunology
at the Academic Medical Center, University of Amsterdam, Amsterdam. He
studies the role of C-type lectin receptors in pathogen interactions and how
these receptors shape adaptive immune responses. Different pathogens such
as HIV-1 and M. tuberculosis subvert the function of C-type lectin receptors to
infect the host. C-type lectin receptor also interact with allergens and can be
important for aberrant immune responses observed during allergy.
Alberto Mantovani is Professor of Pathology at the University of Milan and
Scientific Director of the Istituto Clinico Humanitas. He has contributed to the
advancement of knowledge in the field of Immunology formulating new paradigms and identifying new molecules and functions. As of spring 2014 he has
had over 60.000 citations and has an H-index of 123 (Scopus).
Christian Münz is professor and co-director of the Institute of Experimental
Immunology at the University of Zürich, Switzerland. His lab studies primarily
the immune control of the persistent human tumor virus Epstein Barr virus
and the involvement of macroautophagy in antigen processing for MHC presentation. After obtaining his PhD from the University of Tübingen, Germany,
and his postdoctoral training at the Rockefeller University, New York, USA,
where he became assistant professor, he returned to Europe in 2008 to his
current position.
Claude-Agnès Reynaud is director of research at Institut Necker-Enfants
Malades, Paris Descartes Medical school, and head of the group “Development of the immune system”. She has a long-standing interest in molecular
mechanisms of Ig gene repertoire formation, and more recently extended
the focus of her studies to the functional diversity of B-cell memory/effector
subsets, both in the mouse and in humans.
Seite 8
Magnus Wickman is a board certified paediatrician and paediatric allergologist
with certified training in epidemiology at Karolinska Institutet, Stockholm, Sweden. His work unites population based medicine/epidemiology, clinical medicine in particular food allergy, molecular allergology, and population genetics.
Since1994 until 2014 he has been PI for the Swedish population based birth
cohort BAMSE which started in 1994 and enrolled 4000 new born babies.
Invited Speakers / Vortragende
Maria Yazdanbakhsh is Head of Parasitology at Leiden University Medical Center, The Netherlands, and leads the section “Leiden Immunoparasitology Group”
that works on the immune response to parasites, focusing on immune modulation. Her speciality has been on helminth infections and TH2 responses.
Vortragende am Klinischen Allergietag, 8.11.2014
Prof. Dr. Knut Brockow, Dermatologe und Allergologe aus der Klinik und
Poliklinik für Dermatologie und Venerologie am Biederstein, Technische Universität München, interessiert an Arzneimittelreaktionen, Anaphylaxie und Mastzellerkrankungen wie Mastozytose, bis 2013 über 6 Jahre Präsident der Abteilung “Arzneimittelallergie” der EAACI und beteiligt an vielen Positionspapieren
und Empfehlungen zur Arzneimittelüberempfindlichkeit.
Priv.-Doz. Dr. Jörg Kleine-Tebbe, seit 2002 mit Dr. Gerald Hanf u. Dr. Juliane Ackermann im Allergie- und Asthma-Zentrum Westend (AAZW) in Berlin,
Gemeinschaftspraxis für Allergologie, Dermatologie, Innere Medizin und Umweltmedizin. Besondere Interessen betreffen die Diagnostik und Therapie von
Soforttyp-Allergien und IgE-assoziierten Erkrankungen.
Prof. Dr. med. Dr. phil. Johannes Ring ist Director emeritus Haut und Allergieklinik Biederstein, TU München, die er von 1995 – 2014 leitete. Vorstandsmitglied und Präsident verschiedener allergologischer und dermatologischer
Gesellschaften, u. a. Deutsche Gesellschaft für Allergologie und klinische Immunologie (DGAKI), European Society for Dermatological Research (ESDR),
Collegium Internationale Allergologicum (CIA), European Academy of Dermatology and Venerology (EADV).
Seine Forschungsschwerpunkte umfassen: Entzündliche Hauterkrankungen,
Neurodermitis, Arzneimittel- und Nahrungsmittel-Allergie, Immuntherapie, Allergie und Umwelt. Zur Zeit ist Prof. Dr. med. Dr. phil. Johannes Ring ChiefEditor des Journal European Academy Dermatology Venerology (JEADV).
Univ. Prof. Dr. med. Stingl has contributed greatly to our understanding of
the skin as an immune organ under physiologic and pathologic (e.g. psoriasis, atopic dermatitis, syphilis, HIV-infection) conditions. His major accomplishments include the discovery of Langerhans cells as immunocytes and of the indigenous T cell population of rodent skin. In the recent years, his research group
has elucidated the mode of action of several immunomodulatory drugs. He is a
member of the board of several scientific societies and organizations, advisory
panels, scientific journals and committees, including honorary membership of
the two leading societies of dermatological research, i.e. The Society for Investigative Dermatology and the European Society for Dermatological Research.
He was recently elected a Foreign Associate of the Institute of Medicine of the
US National Academies and holds a membership in the Austrian and German
National Academy of Sciences.
Prof. Dr. med. Margitta Worm wurde 2003 auf die Universitätsprofessur mit
dem Schwerpunkt Immunmodulation allergischer Erkrankungen an der CharitéUniversitätsmedizin Berlin berufen. Aktuell leitet sie die Hochschulambulanz
der Klinik für Dermatologie, Venerologie und Allergologie und die klinisch experimentelle Allergologie in Immunologie des Allergie-Centrums der Charité.
Zu ihren Forschungsschwerpunkten gehören die atopische Dermatitis, Mechanismen der Anaphylaxie, Nahrungsmittelallergie, Immunmodulation allergischer Erkrankungen und die Immunologie von B-Zellen. 2006 hat sie das
deutschsprachige Anaphylaxie-Register initiiert, wo 106 allergologische Zentren
in Deutschland, Österreich und der Schweiz angeschlossen sind. Prof. Dr. med.
Worm ist Vorstandsmitglied der Deutschen Gesellschaft für klinische Immunologie und Allergologie sowie Mitglied in einschlägigen Fachgesellschaften (BDG,
DDG, DGAKI, EAACI) und führt regelmäßig Reviewertätigkeiten für nationale
und internationale Journale durch.
Vortragende der “Nussknacker-Suite”:
OA Dr. Thomas Hawranek • Univ.-Doz. Dr. Wolfgang Hemmer
Ass. Dr. med. Isabelle Pohl • Priv.- Doz. Mag. Dr. Stefan Wöhrl
Seite 9
Exhibitors
ALK-Abelló
Allergie-Service GmbH
Bäckermühlweg 59, 4030 Linz, Austria
www.alk.net/at
www.allergie-plattform.at
Als führender Anbieter von hochqualitativen Produkten zur spezifischen
Diagnose bzw. kausalen Immuntherapie der Typ-I Allergien und als kompetenter Partner von ÄrztInnen und
ApothekerInnen ist es unser zentrales
Anliegen, die Versorgung allergiekranker Menschen durch exzellente
Produkte, Ausbildung und Öffentlichkeitsarbeit zu verbessern und so zu
mehr Gesundheit und Lebensqualität
beizutragen. Als kompetenter Partner
allergologisch tätiger Fachärzte in Österreich entwickeln und vertreiben wir
von ALK-Abelló Allergentherapeutika
zur ursächlichen Behandlung von Allergischer Rhinitis und Konjunktivitis,
allergischem Asthma bronchiale und
allergischen Reaktionen auf Bienenund Wespenstiche. Neben den subkutanen Darreichungsformen stehen
sublinguale Präparate zur Verfügung.
Im Jänner 2007 führten wir als erstes
Unternehmen weltweit die kausale
Tablettenimmuntherapie gegen eine
Gräserpollenallergie ein. Die Produktpalette umfasst weiterhin Allergiediagnostika zur Pricktestung, Intrakutantestung sowie zur nasalen und
konjunktivalen Provokation. Wir von
ALK-Abelló Österreich betreiben in Kooperation mit der ALK-Abelló Zentrale
in Dänemark und mit ALK Deutschland
klinische Forschung auf höchstem Niveau, um die Therapie allergiekranker
Menschen zu verbessern. Wir forschen
ebenfalls im Bereich rekombinanter
Allergene und Adjunvantien, um die
Möglichkeiten der kausalen Allergietherapie zu verbreitern.
Bayer Austria Ges.m.b.H.
Herbststraße 6-10, 1160 Wien
www. bayerhealthcare.at
Bayer HealthCare erforscht, entwickelt, produziert und vertreibt innovative Produkte, um die Gesundheit von
Mensch und Tier weltweit zu verbessern.
Zu seinen Divisionen zählen neben
Pharmaceuticals, Consumer Care,
Animal Health und Medical Care.
Bayer HealthCare ist mit seinen zahlreichen klinischen Studien in den unterschiedlichsten Indikationsgebieten
ein stark vertretenes forschendes
Pharmaunternehmen in Österreich.
Darüber hinaus ist das Unternehmen
in Österreich mit Marketing und Vertrieb befasst.
Mehr unter www.bayerhealthcare.at
Seite 10
BD Life Sciences –
Biosciences
Becton Dickinson Austria GmbH
Concorde Business Park 1/E/1/7
2320 Schwechat, Österreich
Tel.: +43 1 7063660-0
www.bdbiosciences.com
[email protected]
Biosciences bedient den gesamten
Bereich der biologischen und medizinischen Forschung und bietet die
größte Auswahl an innovativen Geräten und Reagenzien für die zelluläre
Analyse an.
Ein breites Spektrum an Analyzern
und Sortern für die Durchflusszytometrie, verbunden mit kompetenter Beratung und Service, ermöglichen die
passgenaue Lösung.für Ihr Labor.
Unser Produktangebot und unsere
Kompetenz machen uns zum interessanten Partner für Forschungs- und
Routinelabors, für die Industrie sowie
für die wachsende Zahl von bio- und
gentechnologischen Einrichtungen.
Für die klinische Durchflusszytometrie stehen gebrauchsfertige, CE-IVD
zertifizierte Lösungen im Bereich der
Immunphänotypisierung von Lymphozyten, Leukämie- und Lymphomdiagnostik, Stammzellenumeration
sowie für die Restzellbestimmung in
Blutprodukten zur Verfügung
Unsere Lösungen zur Automatisierung
der Prozesse ermöglichen eine effizientere Abarbeitung, die hochwertigen
Reagenzien erlauben eine präzisere
Diagnostik für bessere klinische Entscheidungen.
Bencard Allergie GmbH
Lerchenfelder Straße 13/6/42,
1070 Wien, www.bencard.at
Bencard Allergie arbeitet seit 80 Jahren an Lösungen für die spezifischen
Immuntherapie. Es ist uns gelungen,
mit neuen Testverfahren und Produkten die Qualität der Versorgung
allergischer Patienten entscheidend zu
verbessern. 1999 konnten wir unser
Ziel mit der Einführung unseres Produktes POLLINEX® Quattro realisieren. 2004 wurden wir dafür mit dem
MMW-Arzneimittelpreis ausgezeichnet,
eine Auszeichnung für die spezifische
Immuntherapie und speziell für POLLINEX® Quattro. Zahlreiche klinische
Studien unterstreichen die Effektivität
dieses Konzeptes. Wir sind stolz, in
enger Zusammenarbeit mit unseren
Kunden die Zukunft der spezifischen
Immuntherapie aktiv zu gestalten
Biozym Scientific GmbH
Biozym Scientific GmbH, Postfach,
D-31833 Hessisch Oldendorf, Deutsch-
land, Tel:+49 5152-9020,
www.biozym.com
[email protected]
Biozym Biotech Trading GmbH, Wehlistrasse 27b/1/9, A-1200 Wien, Österreich, Tel:+43 1 3340156-0
www.biozym.com, [email protected]
Seit unserer Firmengründung in Hameln 1986 verstehen wir uns als eigenständige und leistungsorientierte
Vertriebs- und Serviceorganisation für
unseren Zielmarkt „ Life Science „ in
Deutschland, Österreich und weiteren
europäischen Ländern.
Unser Produktportfolio umfasst hochleistungsfähige Gerätesysteme, Consumables und Feinchemikalien. Darüber hinaus werden speziell angepasste
Servicedienstleistungen angeboten.
Unsere
molekularbiologischen
Schwerpunkte sehen wir in Anwendungsbereichen
PCR-Technologie,
Next-Generation Sequencing und in
vitro Transkription, sowie Identifizierung und Aufreinigung molekularbiologischer Substanzen.
In Österreich bieten wir exklusiv für
den Bereich Immunologie und Zellbiologie Produkte der Firma Biolegend
an.
Der Vertrieb unserer Produkte erfolgt über ein hoch motiviertes Außendienstteam aus erfahrenen Molekularbiologen und Biochemikern in
Zusammenarbeit mit produktgruppenorientierten Produktmanagern.
eBioscience,
company
an
Affymetrix
Campus Vienna Biocenter 2, 1030 Wien,
Austria, Tel.: +43 1 796 40 40 305,
[email protected]
www.eBioscience.com
eBioscience, an Affymetrix company
ist ein führender Anbieter im Bereich
der Durchflusszytometrie und bietet eine breite Palette an Antikörpern
und Fluorochromen für die Forschung
im Bereich Life Science. Ein weiterer
Schwerpunkt im Portfolio von eBioscience sind klassische, sowie Beadbased Multiplex Immunoassays für
die Quantifizierung von Zytokinen,
Wachstumsfaktoren und weiteren löslichen Proteinen. Neben Assays für die
Quantifizierung von Proteinen werden
auch Reagenzien für die Detektion von
RNA angeboten.
Das Unternehmen entwickelt jedes
Jahr über 800 innovative Produkte für
die Forschung in Immunologie, Onkologie, Zellbiologie und Stammzellenbiologie.
Eubio
Tel.: 0043-1-895 01 45, Schwendergasse 17, 1150 Vienna, Austria
www.eubio.at, [email protected]
Exhibitors
We are a privately owned company in
Vienna, Austria founded by Andreas
Köck in 1995. Our main goal is to provide the Austrian research community
with state-of-the-art Life Science reagents. At the moment our database
and online ordering system contains ~
500.000 products.
Andreas Köck combines more than 30
years of research experience at the
Medical University of Vienna, in the
USA and the Netherlands with several
years of experience in marketing and
business development.
We are the distributing company for
the best original manufacturers of life
science products.
HAL Allergy
Handelsgesellschaft mbH
Johnstrasse 4, A-1150 Wien
Tel:+43 (0) 1 / 985 98 80
E-Mail: [email protected]
Internet: www.hal-allergy.com
HAL Allergy ist einer der führenden Allergenhersteller in Europa mit mehr als
50 Jahren Erfahrung auf diesem Gebiet..Im Jahr 1959 begann HAL Allergy in einem kleinen Labor im Zentrum
von Haarlem in den Niederlanden. Mit
dem Ausbau des Unternehmens zu
einem mittelständischen Pharmaunternehmen wurden die Aktivitäten in
ein größeres Gebäude in Haarlem verlegt.Im Jahr 2009 unternahm das mittlerweile 50 Jahre alte Unternehmen
einen weiteren Schritt und zog um.Die
Architektur des Gebäudes veränderte
sich damit von einem Haus aus den
fünfziger und sechziger Jahren in eine
hochmoderne
Produktionsstätte:In
Bezug auf die Technologie wurden
modernste Anlagen installiert und das
Labor ist jetzt mit fortschrittlicher Laborausrüstung ausgestattet.Hierdurch
kann HAL Allergy seinen zukünftigen
Wachstumsanforderungen
gerecht
werden und seine Mission weiter verfolgen, die Lebensqualität von Allergikern mit Hilfe biopharmazeutischer
Produkte für die ursächliche Behandlung zu verbessern.
Mabtech AB
Box 1233, 131 28 Nacka Strand, Sweden, Tel: +46 8 716 27 00,
[email protected]
www.mabtech.com
Mabtech is a Swedish Biotech company
that produces high quality monoclonal
antibodies and kits for ELISA and ELISpot. We have led the development of
the FluoroSpot assay, which enables
simultaneous analysis of secreted analytes at the single cell level making it
particularly useful when studying polyfunctional T cells or when the supply
of cells is limited. It can also be used
to separately define and enumerate B
cells secreting antibodies of different
isotypes in the same well.
Meda Pharma Gmbh
Guglgasse 15, 1110 Wien,
[email protected], www.meda.at
Meda ist ein global agierendes, führendes Spezialitäten Pharmaunternehmen, das kostengünstige und
zugleich am medizinischen Bedarf orientierte Arzneimittel anbietet. Durch
Einführungen, Weiterentwicklung und
Zukauf innovativer Produkte im Bereich Allergie und Dermatologie versucht Meda ständig den Bedürfnissen
der Patienten gerecht zu werden.
Meda ist eine Niederlassung der Meda
AB., Schweden. Meda ist seit 2005 in
Österreich erfolgreich tätig und setzt
seine Produktschwerpunkte neben den
Bereichen Allergologie und Dermatologie vor allem bei Atemwegserkrankungen, Schmerztherapie, Prävention
und Behandlung von Knochenbruchkrankheiten/Osteoporose,
Mineralstoffwechsel sowie im Fachgebiet der
Gynäkologie.
Im rezeptfreien Apothekenbereich
bietet Meda bewährte Präparate wie
CB12, Naloc, Endwarts, Ce-Limo plus,
Kamillosan, Travelgum sowie Magnofit
direkt an.
Mehr Informationen erhalten Sie unter www.meda.at
Ferdinand Menzl
Medizintechnik GmbH
A-1220 Wien, Donaufelderstrasse
199, Tel: 01 / 2558960-0
www.menzl.com, [email protected]
Ferdinand Menzl Medizintechnik wurde
vor über 25 Jahren als auf Reparaturen
und Wartung von medizintechnischen
Geräten spezialisierter Gewerbebetrieb in Wien gegründet. Im Laufe der
Jahre wurden Handelsbetriebe angegliedert, die sich mit dem Vertrieb
medizintechnischer Geräte zur Therapie und Diagnose von Atemwegserkrankungen befassen sowie auf die
Vermeidung und Sanierung von Allergenen spezialisiert sind. Regelmässige
Teilnahmen an Fortbildungsveranstaltungen und Kongressen halten die
Mitarbeiter auf dem neuesten Stand
und machen sie zu Spezialisten in ihren Tätigkeitsbereichen.
Miltenyi Biotec GmbH
Friedrich-Ebert-Strasse 68, 51429
Bergisch Gladbach, Germany,
Phone: +49220483060
www.miltenyibiotec.com
[email protected]
Miltenyi Biotec is a global provider of
products and services that advance
biomedical research and cellular therapy. Since 1989, we have developed
innovative andreliable technologies
for scientists and clinicians around the
world. Our integrated portfolio of tools
covers techniques of sample preparation, cellseparation, flow cytometry, cell
culture, molecular analysis, and preclinical imaging. Our expertise covers
research areas like immunology, stem
cell biology, neuroscience, and cancer,
and clinical research areas that includehematology, graft engineering, as
well as apheresis. Today, we are more
than 1,300 employees in 22 countries
– all dedicated to empowering scientific discovery and advancing cellular
therapy.
Shire • Medikamente gegen
seltene Erkrankungen
Kärntner Ring 5-7/7. Stock
A-1010 Wien, Tel. 01-205 1160-1051
[email protected], www.shire.at
Seltene Erkrankungen sind häufig genetisch bedingt, mit zunehmenden
Komplikationen verbunden und enden manchmal auch tödlich. Für viele
dieser Erkrankungen gibt es derzeit
keine oder nur eingeschränkte Therapiemöglichkeiten. Shire gelang es bis
heute Medikamente gegen vier seltene genetische Erkrankungen zu entwickeln und auf den Markt zu bringen:
Morbus Hunter, Morbus Fabry, Morbus
Gaucher und hereditäres Angioödem.
Die Entwicklung von Therapien für diese seltenen Erkrankungen ist das Ergebnis langjähriger Forschungsarbeit.
Shire setzt sich mit großem Engagement für die Erforschung und Entwicklung weiterer Therapien im Bereich
der seltenen Erkrankungen ein.
Shire. We enable people with lifealtering conditions to lead better
lives.
STALLERGENES
Österreich GmbH
Mariahilfer Straße 103/1/26, 1060
Wien, Austria,Tel: +43 1 533 74 74-0
[email protected]
www.stallergenes.at
Stallergenes bietet einen ganzheitlichen Ansatz bei allergiebedingten Erkrankungen und stellt Allergologen ein
umfangreiches Produktspektrum von
der Diagnostik bis zur spezifischen
Immuntherapie zur Verfügung.
Mit seinem einzigartigen Know-how
hat sich das Unternehmen unermüdlich der Innovation verschrieben.
Stallergenes leistet damit einen wertvollen Beitrag zur Entwicklung der
spezifischen Immuntherapie und bietet Allergiepatienten immer leistungsfähigere Lösungen.
Seite 11
Oral Presentation 1
<1> Engineering hypoallergenic
variants of the peanut allergens Ara h
2 and Ara h 6
Thomas EIWEGGER (1)*, Merima
BUBLIN(2)*, Klara SCHMIDTHALER(1),
Maria KOSTADINOVA(2), Christian
RADAUER(2), Christine HAFNER(3), Zsolt
SZÉPFALUSI(1), Eva-Maria VARGA(4), Heimo
BREITENEDER(2) *contributed equally
<2> The major cow milk allergen, Bos
d 5, is able to bind siderophore bound
iron and influences T-helper cells
according to its binding state
Heidi A. Müller(1) , Luis. F. Pacios(2),
Cristina Gomez-Casado(2), Hofstetter
G.(1), Georg A. Roth(4), Josef Singer(5),
Araceli Diaz-Perales(2), Erika JensenJarolim(1,5), Roth-Walter F.(1)
<3> Why I? IgE profiling and lifestyle
analysis of 501 Austrian school children
Teresa STEMESEDER(1), Eva
KLINGLMAYR(1), Bettina SCHWEIDLER(1),
Lisa LUEFTENEGGER(2,3), Stephanie
MOSER(4), Roland LANG(3), Martin
HIMLY(1), Gertie J. OOSTINGH(2), Arne
BATHKE(5), Joerg ZUMBACH(4), Thomas
HAWRANEK(3), Gabriele GADERMAIER(1)
<4> Natural clinical tolerance to
peanut in African patients is caused by
poor allergenic activity of peanut IgE
Eva WOLLMANN(1), Carl HAMSTEN
Carl(2,3), Elopy SIBANDA(4), Mary
OCHOME(1), Margarethe FOCKE-TEJKL(1),
Anna ASARNOJ(2,5), Annika ÖNELL(6),
Gunnar LILJA(7), Daniela GALLERANO(1),
Christian LUPINEK(1), Theresa
THALHAMER(8), Richard WEISS(8), Josef
THALHAMER(8), Magnus WICKMAN(7,9),
Rudolf VALENTA(1), Marianne VAN
HAGE(2)
<5> Differences in molecular
sensitization profiles towards animal
allergens revealed by allergen microarray in two generation of patients
with respiratory allergy
Victoria GARIB, Eva WOLLMANN, Rudolf
VALENTA
<6> Preventive sublingual immunotherapy in preschool children: first
evidence for safety and pro-tolerogenic
effects
Christina BANNERT(1), Zsolt
SZÉPFALUSI(1), Leila RONCERAY(1),
Elisabeth MAYER(1), Michaela HASSLER(1),
Eva WISSMANN(1), Eleonora DEHLINK(1),
Saskia GRUBER(1), Alexandra GRAF(2),
Christian LUPINEK(3), Rudolf VALENTA(3),
Thomas EIWEGGER(1),
Radvan URBANEK(1)
Oral Presentation 2
<7> Jagunal-homolog 1 is a critical
regulator of neutrophil function in
fungal host defense
Gerald WIRNSBERGER(1), Florian
ZWOLANEK(2), Johannes STADLMANN(1,3),
Luigi TORTOLA(1), Shang Wan LIU(1),
Thomas PERLOT(1), Päivi JAERVINNEN(4),
Gerhard DUERNBERGER(1,3), Ivona
KOZIERADZKI(1), Renu SARAO(1), Alba
DE MARTINO(5), Kaan BOZTUG(6,7),
Karl MECHTLER(1,3), Karl KUCHLER(2),
Christoph KLEIN(4), Ulrich ELLING(1) and
Josef M. PENNINGER(1)
Seite 12
<8> Mapping of IgG, IgG-subclass,
IgA and IgM reactivity profiles in
African and European HIV-infected
individuals with an HIV-1 clade C
proteome-based array
Daniela GALLERANO(1), Portia NDLOVU(2),
Ian MAKUPE(2), Margarete FOCKETEJKL(1), Kerstin FAULAND(3), Eva
WOLLMANN(1), Elisabeth PUCHHAMMERSTÖCKL(4), Walter KELLER(3), Elopy N.
SIBANDA(5) and Rudolf VALENTA(1)
<9> Identification of a lipid-modifying
enzyme as novel regulator of innate
immune responses
Leonhard X. HEINZ(1), Christoph L.
BAUMANN(1), Marielle KÖBERLIN(1),
Berend SNIJDER(1), Manuela
BRUCKNER(1), Riem GAWISH(1), Omar
SHARIF(1), Kumaran KANDASAMY(1),
Jacques COLINGES(1), Keiryn L.
BENNETT(1), Astrid FAUSTER(1), Guanghou
SHUI(2), Sylvia KNAPP(1), Markus R.
WENK(2) and Giulio SUPERTI-FURGA(1)
<10> Age-related differences
of humoral and cellular immune
responses to primary Japanese
Encephalitis vaccination
A. WAGNER(1), E. GARNER-SPITZER(1), J.
JASINSKA(1), M. PAULKE-KORINEK(1), M.
HOFER(1), K. STIASNY(2), F. X. HEINZ(2),
H. KOLLARITSCH(1), U. WIEDERMANN(1, 3)
<11> The impact of an acute allergic inflammation on neurogenesis and microglia in the hippocampal dentate gyrus
Barbara KLEIN(1,2), Richard WEISS(3),
Sebastien COUILLARD-DESPRES(2,4),
Josef THALHAMER(3), Ludwig AIGNER(1,2)
Oral Presentation 3
<12> Innate responses and antigenpresenting capacity of oral epithelial
cells
Claudia KITZMÜLLER(1), Martina
SCHUSCHNIG(1), and Barbara BOHLE(1)
<13> Phosphorylation of CREB is
upregulated in keratinocytes after
treatment with the major birch pollen
allergen, Bet v 1, and birch pollen lipids
Barbara GEPP(1), Nina LENGGER(1),
Christian RADAUER(1), Florian
GRUBER(2), Michael MILDNER(2), Heimo
BREITENEDER(1)
<14> Epicutaneous application of
recombinant Bet v 1 and Bet v 1
derivatives induces allergen-specific
IgG and T cell responses
RAFFAELA CAMPANA(1), Katharina
MORITZ(2), Angela NEUBAUER(3), Hans
HUBER(3), Rainer HENNING(3), Katharina
BLATT(4), Gregor HOERMANN(5), Tess M.
BRODIE(6), Alexandra KAIDER(7), Peter
VALENT(4), Federica SALLUSTO(6), Stefan
WÖHRL(2), Rudolf VALENTA(1,*)
<15> Azithromycin inhibits IL-1 beta
secretion of innate immune cells
by specificly inhibiting the NLRP3
inflammasome
Guido A. GUALDONI(1), Tilman R.
LINGSCHEID(2), Peter STEINBERGER(1),
Gerhard J. ZLABINGER (1)
<16> Patient-specific immunological
imprint within complex ovarian cancer
tissues
Anastasia MESHCHERYAKOVA(1), Erika
BAJNA(1), Susanne WÖHRER(1)
Elfi SCHARF(1), Martin SVOBODA(1),
Erika JENSEN-JAROLIM(1,2), Georg
HEINZE(3), Peter BIRNER(4), Diana
MECHTCHERIAKOVA(1)
Oral Presentation 4
<17> Carbohydrate coupling as a tool
for modulation of the allergenicity and
immunological properties of the major
birch pollen allergen Bet v 1.0101
MACHADO Yoan(1), MAYR Melissa(1),
THALHAMER Theresa(1), HÖPFLINGER
Veronika(1), SCHEIBLHOFER Sandra(1),
THALHAMER Josef(1), WEISS Richard(1)
<18> Controlling the balance between
effector and regulatory T cells in
peripheral tissues
Douglas F. PINHEIRO(1), Megan M.
MAURANO(1), Abul K. ABBAS(3), Iris K.
GRATZ(1,2,4)
<19> Dual Role of NSAIDs:
overcoming melanoma resistance and
enhancing cytotoxic potential of innate
immune cells
Mariana VÁZQUEZ-STRAUSS, Georg
STINGL
<20> Specific roles for dendritic
cell subsets during initiation and
progression of psoriasis
Elisabeth GLITZNER(1), Ana KOROSEC(1),
Patrick M. BRUNNER(2), Barbara
DROBITS(1), Nicole AMBERG(1), Helia B.
SCHONTHALER(3), Tamara KOPP(2), Erwin
F. WAGNER(3), Georg STINGL(2), Martin
HOLCMANN(1), Maria (1)
<21> The role of Langerhans cells and
natural killer cells in cancer immune
surveillance
Daniela ORTNER(1), Christoph TRIPP(1),
Nicole AMBERG(2), Maria (2), Björn E.
CLAUSEN(3) and Patrizia STOITZNER(1)
Oral Presentation 5
<22> Characterization of the CD8+ T
cell response to allergens
Nazanin SAMADI, Claudia KITZMÜLLER
, Barbara BOHLE, Rene GEYEREGGER,
Beatrice JAHN-SCHMID
<23> Does signal one strength
influence the phenotype and
function of human allergen-specific T
lymphocytes?
Martín R. CANDIA(1), Peter TAUBER(1),
Alina NEUNKIRCHNER(1,2), Doris
TRAPIN(1), Sandra ROSSKOPF(1),
Peter STEINBERGER(1) and Winfried F.
PICKL(1,2).
<24> Nitrated Beta-Lactoglobulin
enhances the anaphylactic response in
a murine food allergy model
Susanne C. DIESNER(1,2), Cornelia
SCHULTZ(1), Chloé ACKAERT(3), Gertie
J. OOSTINGH(4), Anna ONDRACEK(1),
Caroline STREMNITZER(1), Denise
HEIDEN(1), Josef SINGER(1),
Franziska ROTH-WALTER(1,5), Judit
FAZEKAS(1), Thomas EIWEGGER(2),
Zsolt SZÉPFALUSI(2), Erika JENSENJAROLIM(1,5), Ernst-Hanno
STUTZ(3), Albert DUSCHL(3) and Eva
UNTERSMAYR(1)
<25> The trimeric complex of
recombinant CD23 together with
allergen and allergen-specific IgE
Regina M. Selb(1), Julia EcklDorna(1), Christian Lupinek(2), Birgit
Linhart(2), Andrea Teufelberger(3),
Walter Keller(3), Kenneth H. Roux(4),
Rudolf Valenta(2) and Verena
Niederberger(1)
<26> Complement opsonization of
A.fumigatus modifies dendritic cell
maturation and up-take
Marion STEGER(1), Emina JUKIC(1),
Wilfried POSCH(1), Cornelia LASSFLÖRL(1), Hubertus HAAS(2), Doris
WILFLINGSEDER(1)
<27> Failure of specific
immunotherapy (SIT) with house
dust mite (HDM) allergen extracts due
to lack of HDM allergens capable of
inducing specific IgG responses in the
therapeutic extracts
Kuan-Wei CHEN (1), René ZIEGLMAYER
(2), Petra ZIEGLMAYER (2), Patrick LEMELL
(2), Friedrich HORAK (2), Rudolf VALENTA
(1), Susanne VRTALA (1)
Oral Presentation 6
<28> Signaling capacities of the IL-31
receptor complex
Michaela MITTERMEIR, Elisabeth MAIER,
Stefanie ESS, Albert DUSCHL, Jutta
HOREJS-HOECK
<29> Bidirectional polarization of T
cell function via CD43
Madhura MODAK, Petra CEJKA, Petra
WAIDHOFER-SÖLLNER, Sabrina JUTZ, Otto
MAJDIC, Peter STEINBERGER, Gerhard
ZLABINGER, Johannes STÖCKL
<30> Memory T cells and plasma cells
niches in human bone marrow
L. PANGRAZZI, B. Jenewein, J. Lair, M.
Krismer, B. Weinberger, B. GrubeckLoebenstein
<31> The urokinase receptor as a
positive regulator of T cell activation
Alexander ZWIRZITZ(1), Karin
PFISTERER(1), Vladimir LEKSA(2) and
Hannes STOCKINGER(1)
<32> Molecular analysis of MAZR
function in CD4+ T cells
Liisa ANDERSEN, Alexandra SCHEBESTA,
Alexandra GÜLICH, Shinya SAKAGUCHI
and Wilfried ELLMEIER
<33> Structural and functional
rejuvenation of the aged brain by an
approved anti-asthmatic drug
Julia MARSCHALLINGER(1,2), Barbara
KLEIN(1,2), Iris Schäffner (3,4), Sébastien
COUILLARD-DESPRES(2,5), Claudia
SCHMUCKERMAIR(6), D. Chichung Lie
(3,4), Nicolas SINGEWALD (6), Ludwig
AIGNER(1,2)
Poster Session 1.1
<34> Identification of linear and
conformational epitopes of bovine
alpha -lactalbumin
Yuan SHUILIN, Li XIN, Chen HONGBING,
Gao JINYAN, Wu ZHIHUA, Yang ANSHU,
Tong PING(1,2)
<35> In-print of the environment on the
molecular sensitization profile towards
pollen allergens revealed by allergen
micro-array.
Viktoriya GARIB (1), Eva WOLLMANN (1),
Gulnara DJAMBEKOVA (2), Rudolf VALENTA
<36> Characterization of recombinant
gamma-gliadin protein and its
evaluation for diagnosis of wheat
hypersensitivities
Bharani Srinivasan1, Margarete Focke-Tejkl1,
2, Milena Weber1, Sandra Pahr1, Alexandra
Baar1, Michael Hertl3 , Raja Atreya4,
Markus.F.Neurath4, Harald Vogelsang5,
Wolf-Dietrich Huber6, Rudolf Valenta1, 2
<37> Construction of a phage display
library from Escherichia coli to study
IgE-reactive bacterial antigens.
Sheron DZORO, Irene MITTERMANN,
Rudolf VALENTA
<38> The immune response against
the timothy grass pollen allergen Phl p
5 in non-allergic humans depending on
different environments
Almedina ISAKOVIC, Christoph
HILLEBRAND, Theresa THALHAMER,
Sandra SCHEIBLHOFER, Josef THALHAMER,
Richard WEISS
<39> Immunogenicity of the major
peach allergen
Pru p 3: Does protein conformation,
physico-chemical properties and
stability matter?
Stephanie EICHHORN(1), Isabel
PABLOS(1), Serge VERSTEEG(2), Laurian
ZUIDMEER-JONGEJAN(2), Ronald VAN
REE(2), Fatima FERREIRA(1), Gabriele
GADERMAIER(1)
<40> ImmunoCAP cellulose displays
cross-reactive carbohydrate epitopes
and can cause false-positive test
results in patients with anti-CCD IgE
antibodies
Wolfgang HEMMER(1), Stefan WÖHRL(1),
Felix WANTKE(1), Friedrich ALTMANN(2)
<41> Investigation of the structural
and immunological behavior of Art v 3
upon thermal treatment
Sabrina WILDNER(1,2), Lorenz
STOCK(2,3), Adriano MARI(4),
Hanno STUTZ(2,3) and Gabriele
GADERMAIER(1,2)
<42> Characterization and IgE epitope
mapping of Tri a 37, a serological
marker for severe wheat food allergy
Sandra PAHR(1,2), Regina SELB(3),
Claudia CONSTANTIN(1), Milena
WEBER(1), Margit FOCKE-TEIJKL(1),
Gerhard HOFER(4), Andela DORDIC(4),
Walter KELLER(4), Nikolaos G.
PAPADOPOULOS(5), Stavroula GIAVI(5),
Mika MÄKELÄ(6), Anna PELKONEN(6),
Verena NIEDERBERGER(3), Susanne
VRTALA(1,2), Rudolf VALENTA(1)
<43> Analysis of interactions of the
major birch pollen allergen Bet v 1
with naturally occurring and synthetic
ligands
Lorenz AGLAS(1), Claudia ASAM(1),
Stefanie GILLES(2), Claudia TRAIDLHOFFMANN(2), Fatima FERREIRA(1),
Michael WALLNER(1)
<44> Structural and immunological
study of allergenic defensin-like
proteins from mugwort, ragweed and
feverfew
Isabel PABLOS(1), Stephanie
EICHHORN(1), Peter BRIZA(1), Christof
EBNER(2), Naveen ARORA(3), Stefan
VIETHS(4), Gabriele GADERMAIER(1),
Fatima FERREIRA(1)
<45> Production and characterization
of recombinant Per a 1, a major
allergen of Periplaneta americana
Bianca KASTNER(1), Stephanie
EICHHORN(1), Isabel PABLOS(1), Sabrina
WILDNER(1), Ines FORSTENLEHNER(2),
Stefan VIETHS(3), Naveen ARORA(4),
Gabriele GADERMAIER(1), Fatima
FERREIRA(1)
<46> Renaissance of a well-known
contact-allergen
Tamar KINACIYAN
<47> Recognition of birch pollen allergen Bet v 1 by endolysosomal proteases
Regina FREIER and Hans BRANDSTETTER
<48> Investigation of indoor allergen
exposure and IgE sensitization
Bettina SCHWEIDLER(1), Teresa
STEMESEDER(1), Eva KLINGLMAYR(1), Lisa
LÜFTENEGGER(2,3), Stephanie MOSER(4),
Roland LANG(2), Martin HIMLY(1), Gertie
J. OOSTINGH(3), Arne BATHKE(5), Jörg
ZUMBACH(4), Thomas HAWRANEK(2),
Gabriele GADERMAIER(1)
<49> Proteomic characterization of
the Blomia tropicalis allergen Blo t 2
Juan R URREGO(1), João PONTE(1),
Michael WALLNER(2), Carina PINHEIRO(1),
Neuza ALCANTâRA-NEVES(1), Peter
BRIZA(2), Fátima FERREIRA(2)
<50> Stability and microheterogeneity of Cor a 14, the 2S
albumin from hazelnut
Sabine PFEIFER(1), Pawel DUBIELA(1),
Merima BUBLIN(1), Karin HUMMEL(2),
Christine HAFNER(1,3), Karin HOFFMANNSOMMERGRUBER(1)
Poster Session 1.2
<51> Biomarkers of Infallation in
juvenile idiopathic arthritis (JIA)
Juergen Brunner(1), Thomas Giner(1),
Guenter Weiss(2), Dietmar Fuchs(3)
<52> The Toll-like receptor 4 agonist
MRP8/14 protein complex (Calprotectin)
in autoinflammation: Potential
biomarker in chronic nonbacterial
osteomyelitis – a case report
Jürgen Brunner(1)
<53> Interleukin 1 blockade with canakinumab for Hyper IGD syndrome (HIDS)
Jürgen Brunner(1), Elisabeth
Binder(1), Daniela Karall(1), Johannes
Zschocke(2), Christine Fauth(2)
<54 Complement analysis in patients
with Juvenile Idiopathic Arthritis
(WIELISA, SC5b9-ELISA)
T. Giner(1), L. Hackl(1), R.
Würzner(2), J. Brunner(1)
<55> Functional analyses of total
complement activity in an ELISAbased kit which replaces haemolytic
assays: a decade of experience and
future perspectives
Reinhard WÜRZNER(1), Tom Eirik
MOLLNES(2), Francesco TEDESCO(3),
Peter GARRED(4), Lennart TRUEDSSON(5),
Malcolm W. TURNER(6), Moh R. DAHA(7),
Robert B. SIM(8)
<56> Reactive oxygen species
mediated regulation of linker for
activation of T cells in autoimmunity
Florian FORSTER(1), Clara MARQUINA(1),
Bernhard MALISSEN(2), Rikard
HOLMDAHL(1)
<57> Serum markers of
antiphospholipid syndrome detection
and their diagnostic significance in the
pediatric practice
Anna BATYROVA, Irina KONDRAKHINA,
Olga KOZHEVNIKOVA, Anna GEVORKYAN
<58> Complement-opsonized HIV
overcomes SAMHD1 restriction in DCs
Wilfried POSCH(1), Marion STEGER(1),
Ulla KNACKMUSS(1), Felipe DIAZGRIFFERO(2), Cornelia LASS-FLÖRL(1),
Arnaud MORIS(3), Oliver T. KEPPLER(4),
Doris WILFLINGSEDER(1)
1st author = presenting author exept when underlined • abstracts/affiliations in the digital abstractbook at www.oegai.org
Seite 13
<59> Triggering CD11b/c on DCs
promotes immediate Th17 polarization
during acute HIV-1 infection
Wilfried POSCH(1), Andrea SCHROLL(2),
Asier SAEZ-CIRION(3), Gianfranco
PANCINO (3), Teunis GEIJTENBEEK(4),
Cornelia LASS-FLÖRL(1), Günter
WEISS(2), Doris WILFLINGSEDER(1)
<60> Evaluation of vaccine
responsiveness against tick-borne
encephalitis (TBE) and hepatitis A
in allergic patients – differences to
healthy controls?
Erika GARNER-SPITZER(1), Michael
HOFER(1), Reinhard JARISCH(2), Tamar
KINACIYAN(3), Michael KUNDI(4), Ursula
WIEDERMANN(1)
<61> SOD1 Protects From Type I
Interferon-Driven Oxidative Damage
in Viral Hepatitis
Anannya BHATTACHARYA*(1),
Ahmed N. HEGAZY*(2,3,4), Nikolaus
DEIGENDESCH**(5), Lindsay
KOSACK**(1), Jovana CUPOVIC(6),
Richard K. KANDASAMY(1), Andrea
HILDEBRANDT(1), Doron MERKLER(7),
Anja A. KÜHL(8), Christopher
SCHLIEHE(1), Isabel PANSE(2,3), Bojan
VILAGOS(1), Kseniya KHAMINA(1),
Isabelle ARNOLD(4), Lukas FLATZ(6),
Haifeng C. XU(9), Philipp A. LANG(9),
Alan ADEREM(10), Giulio SUPERTIFURGA(1), Jacques COLINGE(1), Burkhard
LUDEWIG(6), Max LÖHNING(2,3),†,
Andreas BERGTHALER(1),†
<62> Comparison of the
immunogenicity and reactogenicity
after subcutaneous (s.c.) or intra
muscular (i.m.) vaccination with a
tick-borne encephalitis vaccine
Stefan HOPF(1), Erika GARNERSPITZER(1), Michael HOFER(1), Ingrid
DEMEL(1), Michael KUNDI(2), Otfried
KISTNER(3) and Ursula WIEDERMANN(1)
<63> STAT1 in myeloid cells is
required to limit early replication and
persistence of murine cytomegalovirus
in vivo
Mario BIAGGIO(1), Caroline LASSNIG(1,2),
Rita ROM(1), Astrid KRMPOTIC(3), Stipan
JONJIĆ(3), Birgit STROBL(1) and Mathias
MÜLLER(1,2)
Poster Session 1.3
<64> T cell- independent boost of
Memory IgE responses by B cell
epitopes
Meena NARAYANAN(1), Margarete FOCKETEJKL(2), Rudolf VALENTA(1,2), Birgit
LINHART(1)
<65> House dust mite extract is a
robust source of enzymes that impair
epithelial barrier function
K. Oida (1,2), L. Einhorn (1,3), S. Vrtala
(4,5), Y. Resch (4), L. Panakova (6), F.
Roth-Walter (1), J. Fazekas (1,3), H.
Matsuda (2), A. Tanaka (7), E. JensenJarolim (1,3)
<66> Rise of total IgE levels upon
omalizumab treatment is not due to
activation of IgE+ memory B cells
Julia ECKL-DORNA (1), Renate FRÖSCHL
(1), Christian LUPINEK (1), Renata KISS
(1), Katharina MARTH (1), Raffaela
CAMPANA (1), Katharina BLATT (1), Peter
VALENT (1), Regina M. SELB (1), Andrea
MAYER (1), Katharina GANGL (1), Irene
STEINER (1), Philippe GEVAERT (2), Rudolf
VALENTA (1), Verena NIEDERBERGER (1)
Seite 14
<67> Hypoxia contributes to
melanoma phenotype change by
affecting the response to vemurafenib
Daniela PUCCIARELLI(1), Nina
LENGGER(1), Martina TAKÁČOVÁ(2),
Heimo BREITENEDER(1), Silvia
PASTOREKOVA(2), Christine HAFNER(1,3)
<68> Novel approach for combined
treatment of birch pollen and
associated food allergies
Heidi HOFER(1), Claudia ASAM(1), Michael
HAUSER(1), Peter BRIZA(1), Christof
EBNER(2), Fatima FERREIRA(1), Michael
WALLNER(1)
<69> Allergen specific antibody
responses in non-atopic humans.
Implications for antigen uptake and
dendritic cell polarization
Christoph HILLEBRAND, Almedina
ISAKOVIC, Josef THALHAMER, Richard
WEISS
<70> Monitoring the induction of blocking
antibodies during birch pollen AIT
Sara HUBER(1), Heidi Hofer(1), Roland
LANG(2), Thomas HAWRANEK(2), Michèle
RAUBER(3)(4), Fatima FERREIRA(1),
Michael WALLNER(1)
<71> Codon harmonization enhances
heterologous expression of Bet v 1 in
E. coli
Maria Alejandra PARIGIANI(1), Yoan
MACHADOf(1), Sabrina WILDNER(1),
Peter BRIZA(1), Lorenz AGLAS(1), Martin
WOLF(1), Fátima FERREIRA (1), Michael
WALLNER(1)
<72> Role of allergen-based
component-divided diagnostics in
choice of allergy therapy approach for
children with pollinosis
M.A SNOVSKAYA., L.S. NAMAZOVABARANOVA, O.V. KOZEVNIKOVA, A.K.
GEVORKYAN
<73> Immunity towards neo-antigen
in skin grafts: Mouse models for skin
gene-therapy
Sophie KITZMUELLER(1,2), Douglas
PINHEIRO(1), Thomas KOCHER(2), Johann
BAUER(2), Iris GRATZ(1,2,3)
<74> The immune response to
laminin 5 in skin gene therapy in
epidermolysis bullosa
Ana I. SANCHO(1,2), Maria M. KLICZNIK(1),
Johann W. BAUER(2), Iris K. GRATZ(1,2,3)
<75> Neuraminidase-coated, allergenloaded microparticles are a safe and
efficient novel food allergy treatment option
Susanne C. DIESNER(1,2), Cornelia
SCHULTZ(1), Xue-Yan WANG(3), Katharina
BEITL(1), Franziska ROTH-WALTER(1,4),
Denise HEIDEN(1), Anna ONDRACEK(1),
Josef SINGER(1), Judit FAZEKAS(1),
Caroline STREMNITZER(1), Thomas
EIWEGGER(2), Zsolt SZÉPFALUSI(2),
Isabella PALI-SCHÖLL(1,4), Erika JENSENJAROLIM(1,4), Franz GABOR(3) and Eva
UNTERSMAYR(1)
<76> Development of a humanized
mouse model to study the immune
response to skin gene therapy in
epidermolysis bullosa (EB)
Maria M KLICZNIK(1), Eva MURAUER(2),
Iris K GRATZ(1,2,3)
<77> Novel meta-analysis of gene
expression in mouse allergic asthma
Berislav BOSNJAK*(1), Michela RIBA*(2),
Jose Manuel GARCIA-MANTEIGA*(2),
Michelle M. EPSTEIN*(1), Elia STUPKA*(2)
<78> 5- and 10-year post-relapse
survival of pediatric and young adult
sarcoma patients after a dendritic cellbased cancer immunotherapy.
Friedrich ERHART(1), Alexander M.
DOHNAL(1), Thomas FELZMANN(2), Philipp
FUNOVICS(3), Leo KAGER(4,5), Volker
WITT(4,5), Susanna LANG(6), Carmen
VISUS(2)
<79> Can225IgG, a new canine antiEGFR antibody
Judit FAZEKAS(1,2), Josef
SINGER(1,2), Wei WANG(3), Marlene
WEICHSELBAUMER(1), Alexander
MADER(4), Miroslawa MATZ(1), Willibald
STEINFELLNER(4), Yuri SOBANOV(1),
Diana MECHTCHERIAKOVA(1), Michael
WILLMANN(5), Edzard SPILLNER(6),
Renate KUNERT(4), Erika JENSENJAROLIM(2,1).
<80> Neonatal colonization with
recombinant lactic acid bacteria for
prevention of poly-sensitization
Priya SARATE(1), Stefan HEINL(2), Hana
KOZÁKOVA(3), Reingard GRABHERR(2),
Irma SCHABUSSOVA(1), Ursula
WIEDERMANN(1)
<81> Immune alterations after
thymectomy in early childhood
Manuela ZLAMY(1), Reinhold WÜRZNER(2),
Walther PARSON(3), Heidemarie
HOLZMANN(4), Verena JELLER(1), Martina
PRELOG(5)
<82> Towards a non-allergenic
peptide mix containing the T cell
epitopes of relevant house dust mite
allergens
Huey-Jy HUANG(1), Mirela CURIN(1),
Srinita BANERJEE(1), Kuan-Wei CHEN(1),
Tetiana GARMATIUK(1), Yvonne
RESCH(1), Raffaela CAMPANA(1),
Margarete FOCKE-TEJKL(1), Rudolf
VALENTA(1), Susanne VRTALA(1,3)
Poster Session 2.1
<83> The fibroblast network serves
as guiding structure for directed
monocyte migration in 3D synovial
tissue cultures
Ruth BYRNE(1), Karolina VON
DALWIGK(1), Günter STEINER1, Johannes
HOLINKA2, Reinhard WINDHAGER2, Josef
S. SMOLEN1, Hans KIENER1, Clemens
SCHEINECKER(1)
<84> Selective activation of
cannabinoid receptor 2 primes
eosinophils for enhanced migratory
responsiveness
Robert FREI, Gerald PARZMAIR, Silke
SCHRANZ, Akos HEINEMANN, Eva STURM
<85> Dendritic cells use IgE-mediated
antigen cross-presentation to generate
cytotoxic T cells in response to low
dose soluble antigen
Barbara PLATZER (1), Kutlu G. ELPEK
(2), Viviana CREMASCO (2), Kristi BAKER
(3), Cornelia SCHULTZ (1, 4), Eleonora
DEHLINK (1, 5) Kai-Ting C. SHADE (6),
Robert M. ANTHONY (6), Richard S.
BLUMBERG (3), Shannon J. TURLEY (2)
and Edda FIEBIGER (1)
<86> HAX1 deletion impairs BCRinternalization, leading to delayed
apoptosis of mature B cells
Gertrude ACHATZ-STRAUSSBERGER
<87> EGFR is required in liver
macrophages for IL-1-induced
IL-6 production and hepatocellular
carcinoma formation
Hanane LANAYA(1)*, Anuradha
NATARAJAN(1)*, Karin KOMPOSCH(1)*,
Liang LI(2), Nicole AMBERG(1),
Stefanie K. WCULEK(1), Martina
HAMMER(1), Rainer ZENZ(1), Markus
PECK-RADOSAVLJEVIC(3), Wolfgang
SIEGHART(3), Michael TRAUNER(3),
Hongyang WANG(2), Maria SIBILIA(1)
<88> Inducible Neo-Antigen
Expression in Steady State.
Langerhans Cells mediates
Immunological Tolerance
Helen STRANDT(1), Veronika
HÖPFLINGER(1), Peter HAMMERL(1),
Daniel H. KAPLAN (2), Dagmar WIRTH(3),
Josef THALHAMER(1), Angelika
STOECKLINGER(1)
<89> Elucidating the effects of
costimulation blockade on alloreactive cytotoxic T cells
Silke SCHROM(1), Sarah AHMADI(1),
Barbara DILLINGER(1), Wolfgang
HOLTER(1,2), Alexander DOHNAL(1),
Andreas HEITGER(1,2)
<90> The role of RGS16 in immune
regulation
Bastien A. HUBER(1), Angela
HALFMANN(1), Klara SOUKUP(1),
Alexander M. DOHNAL(1)
<91> Migratory skin dendritic cells
are involved in CD8+ T cell responses
against the melanoma-associated
antigen gp100
David G. MAIRHOFER(1), Vincent
FLACHER(2), Christoph H. TRIPP(1), Björn
E. CLAUSEN(3), Suzie CHEN(4), Patrizia
STOITZNER(1)
<92> T cells from Multiple Myeloma
patients exhibit features of T-cell
exhaustion
Claudia ZELLE-RIESER(1),
Shanmugapriya THANGAVADIVEL(1),
Wolfgang WILLENBACHER (2), Rainer
BIEDERMANN(3), Richard GREIL(1,4) and
Karin JÖHRER(1)
<93> The role of Langerin-positive
skin dendritic cells in chemical skin
carcinogenesis
Christoph H. TRIPP(1), Daniela
ORTNER(1), Sandrine DUBRAC(1), David E.
SCHLÖGL(1), Kerstin KOMENDA(1), Björn
E. CLAUSEN(2) and Patrizia STOITZNER(1)
<94> Lowering T cell activation
strength in vivo polarizes T cell
differentiation towards a regulatory
phenotype
Douglas F. PINHEIRO(1), Sophie
SKITZMUELLER(1,3), Maria Magdalena
KLICZNIK(1,3), Gertrude ACHATZ(1), Abul
K.ABBAS(2), Iris GRATZ(1,3,4).
Poster Session 2.2
<95> Multi-sensitization to
hymenoptera venoms
Karine MARAFIGO DE AMICIS (1,2,6);
Alexandra SAYURI WATANABE (2,3); Clovis
Eduardo GALVAO (2,4); Daniele DANELLA
FIGO (1,2); José Roberto APARECIDO
DOS SANTOS-PINTO (2,5); Mario Sergio
PALMA (2,5); Fábio FERNANDES MORATO
CASTRO (1,2,3); Jorge KALIL (1,2,3,4);
Fatima FERREIRA–BRIZA (6); Gabriele
GADERMAIER (6); Keity SOUZA SANTOS
(1,2);
<96> Beside Der p 1 and Der p 2, also
other house dust mite allergens have
high allergenic activity
Yvonne RESCH(1), Mira ŠILAR(2), Peter
KOPAČ(2), Mihaela ZIDARN(2), KuanWei CHEN(1), Wayne THOMAS(3), Peter
KOROŠEC(2), Mitja KOŠNIK(2), Rudolf
VALENTA(1) and Susanne VRTALA(1,4)
<97> Expression of recombinant
canine, feline and equine FcepsilonRIalpha chains for improved IgE profiling
in these species
Lukas EINHORN(1,2), Judit FAZEKAS(1,2),
Martina MUHR(1,2), Alexandra
SCHOOS(1,2), Lucia PANAKOVA(3),
Krisztina MANZANO-SZALAI(1), Kumiko
OIDA(1,4), Josef SINGER(2), Erika
JENSEN-JAROLIM(1,2)
<98> High density IgE recognition
of the major grass pollen allergen
Phl p 1 revealed with single chain
IgE antibody fragments obtained by
combinatorial cloning
Christoph MADRITSCH(1), Elisabeth
GADERMAIER(1), Uwe RODER(2), Christian
LUPINEK(1), Rudolf VALENTA(1) and
Sabine FLICKER(1)
<99> Generation of new cassette
vectors for the targeted presentation
of human-relevant antigens
(allergens) in humanized mouse
models
Bernhard KRATZER(1), Alina
NEUNKIRCHNER(1,2), Winfried F.
PICKL(1,2)
<100> Identification and
characterization of natural adjuvants
in birch pollen
Dagmar WERNER, Birgit NAGL, Barbara BOHLE
<101> The role of neutrophils in IgEmediated allergy
Dominika POLAK, Birgit NAGL, Claudia
KITZMÜLLER, Barbara BOHLE
<102> Cor a 8 displays reduced
stability upon heat and digestion
treatment
Pawel DUBIELA(1), Sabine PFEIFER(1),
Merima BUBLIN( 1, 2), Christine
HAFNER(1),
Karin HOFFMANN-SOMMERGRUBER(1)
Poster Session 2.3
<103> HIV opsonization modulates
DC signaling
Ulla KNACKMUSS(1), Wilfried POSCH(1),
Marion STEGER(1), Michael BLATZER(1),
Kristian PFALLER(2), Cornelia LASSFLÖRL(1), Doris WILFLINGSEDER(1)
<104> Interleukin-2/antiinterleukin-2 antibody complexes
expand T regulatory cells and protect
against allergen-induced airway
hyperreactivity
Alina NEUNKIRCHNER(1,2), Daniela
WOJTA-STREMAYR(1,2), Klaus G.
SCHMETTERER(2), Lukas MAGER(2)
Victoria REICHL(1,2), Edward
ROSLONIEC(3), Ronald NAUMANN(4),
Gerhard DEKAN(5), Beatrice JAHNSCHMID(6), Barbara BOHLE(1,6) and
Winfried F. PICKL(1,2)
<105> Resveratrol intake enhances
indolamine-2,3-dioxygenase activity in
humans
Guido A. GUALDONI(1), Katharina A.
MAYER(1), Johanna M. GOSTNER(2),
Dietmar FUCHS(3), Gerhard J.
ZLABINGER(1)
<106> The CD58-CD2 axis is the
primary costimulatory pathway in
human CD28 negative CD8 T cells
Judith LEITNER(1), Dietmar HERNDLERBRANDSTÄTTER(2), Beatrix GRUBECKLOEBENSTEIN(2), Gerhard ZLABINGER(1),
Peter STEINBERGER(1)
<107> Basophils from house dust
mite-allergics show an altered TLR
profile from birch pollen- or nonallergic individuals
Markus STEINER(1), Thomas HAWRANEK(2),
Michael SCHNEIDER(3), Andrea HARRER(2),
Jutta HOREJS-HOECK(1), Fatima
FERREIRA(1), Martin HIMLY(1)
<108> The soluble cytoplasmic tail
of CD45 (ct-CD45) induces quiescent
anergy in human T cells
Alexander PUCK, Maria SEYERL, Stefan
HOPF, Otto MAJDIC, Gerhard
ZLABINGER, Judith LEITNER, Peter
STEINBERGER, Johannes STÖCKL
<109> The anti-malarial drugs
chloroquine and hydroxy-chloroquine
show suppressive potency on purified
human CD4+ T-cells
Ralf SCHMIDT(1), Franz RATZINGER(1),
Sabrina JUTZ(2), Peter STEINBERGER(2),
Winfried F. PICKL(2) and Klaus G.
SCHMETTERER(1)
<110> STAT3 governs granzyme B
and IL-10 production in CD4+ T-cells
Klaus G. SCHMETTERER(1,2), Alina
NEUNKIRCHNER(1), Daniela WOJTASTREMAYR(1) Judith LEITNER(1), Peter
STEINBERGER(1), and Winfried F. PICKL(1)
<111> Endotoxin contaminations in
recombinant proteins activate primary
human CD1c+ dendritic cells
Harald SCHWARZ, Maria SCHMITTNER,
Albert DUSCHL, Jutta HOREJS-HOECK
<112> Generation of a multiparameter reporter T cell line
Sabrina JUTZ(1), Sandra
ROSSKOPF(1), Judith LEITNER(1),
Klaus SCHMETTERER(2), Katharina
GRABMEIER-PFISTERHAMMER(3), Peter
STEINBERGER(1)
<113> Azithromycin suppresses CD4+
T-cell activation by direct modulation
of mTOR activity
Franz RATZINGER(1), Helmuth
HASLACHER(1), Wolfgang POEPPL(2), Gregor
HOERMANN(1), Johannes J KOVARIK(3),
Heinz BURGMANN(2), Wolfgang F PICKL(4)
and Klaus G SCHMETTERER(1)
<114> The impact of NOD1 on IL-10
signaling
Theresa NEUPER, Albert DUSCHL and Jutta
HOREJS-HOECK
<115> The tryptophan metabolite
picolinic acid suppresses proliferation
and metabolic activity of CD4+ T-cells
Johanna PRODINGER(1), Julia LOACKER(1),
Ralf SCHMIDT(1) Franz RATZINGER(1),
Gregor HÖRMANN(1), Winfried F. PICKL(2)
and Klaus G. SCHMETTERER(1)
Sparkling Science Poster
<116> ALRAUNE - Allergy Research in
Rural, Alpine and Urban Networks
David SCHWARZENBACHER(1)*, Julia
ZLOEBL(1)*, Teresa STEMESEDER(2), Eva
KLINGLMAYR(2), Edith OBERKOFLER(1),
Gabriele GADERMAIER(2)
1st author = presenting author exept when underlined • abstracts/affiliations in the digital abstractbook at www.oegai.org
Seite 15
Austrian Society for Allergology and Immunology, Nov 6 - 8, 2014, Salzburg
Opening
Keynote Lecture
Abstract
Autophagy-mediated antigen presentation
Christian Münz
Viral Immunobiology, Institute for Experimental Immunology, University of Zürich, Switzerland
Antigen preservation for presentation is a hallmark of potent antigen presenting cells. We could
show that in human macrophages and dendritic cells, a subset of phagosomes gets coated
with Atg8/LC3, a component of the molecular machinery of the cellular catabolic pathway
macroautophagy, and maintains phagocytosed antigens for prolonged presentation on MHC
class II molecules. These Atg8/LC3 positive phagosomes are formed around antigen with TLR2
agonists and require ROS production by NOX2 for their generation. A deficiency in the NOX2
dependent formation of these antigen storage phagosomes could contribute to compromise
anti-fungal immune control in chronic granulomatous disease (CGD) patients. While, thus, a
role of the macroautophagy machinery for extra- and intracellular antigen presentation on MHC
class II molecules has been established, the role of this pathway for MHC class I presentation
to CD8+ T cells remains largely unexplored. We could demonstrate that macroautophagy
deficiency in dendritic cells leads to an enhanced CD8+ T cell priming during influenza A virus
infection in vivo, resulting in decreased pathology. This increased CD8+ T cell stimulation
is caused by elevated MHC class I surface levels in macroautophagy deficient cells. While
MHC class I expression and antigen processing seems unaffected, MHC class I molecules are
stabilized on the cell surface of macroautophagy deficient cells due to decreased internalization
and degradation. These findings suggest that stimulation of macroautophagy to harness its
pathogen degrading functions should be explored with caution, since it could compromise
priming of CD8+ T cell responses.
Invited by FWF PhD Program W1248: Molecular, Cellular and Clinical Allergology (MCCA)
(Coordinator: Winfried F. Pickl)
- 16 -
1st author = presenting author except when underlined
Magnus Wickman
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Keynote Lecture
Background: Allergic sensitisation is not necessary related to current or later onset of allergyrelated diseases. The search for sensitisation patterns of allergen molecules early in life related
to the trajectories of asthma, rhinitis and eczema is warranted. The aim of this study was to
evaluate the role of IgE to microarrayed allergen molecules using longitudinal data of a large
birth cohort in relation to onset, persistence and/or disappearance of allergy related diseases
among children followed from 4 to 16 years.
Abstract
Childhood-to-adolescence evolution of allergenspecific IgE antibodies
Methods: Questionnaire data and sera from follow-ups at 4, 8 and 16 years in a large
population based birth cohort (BAMSE) were used. Sera were available from all three time
points in 1699 children. A random sample of 786 of these children was used for IgE analyses
to 140 allergen components using an allergen-chip based on ISAC technology developed in the
MeDALL FP7-funded research program. Asthma, rhinitis and eczema (A, R and E) were defined
from questionnaire data.
Results: IgE reactivity to the majority of all allergen molecules increased over time
irrespective of current asthma, rhinitis or eczema. However, differences were seen in the
evolution of IgE in particular for airborne allergens components compared to peanut allergen
components. We sought to identify key allergen molecules as well as bystander molecules.
At 4 years 5.2% were sensitized to 41 molecules with an absolute risk of 90% to have onset
of asthma or rhinitis after 4 year. For eczema no such molecules could be identified. Specific
allergy in relation to PR-10, cat and dog allergen molecules has been investigated.
Conclusions: Analysis of IgE to microarrayed allergen components seems to be a promising
tool in predicting onset and persistency of asthma or rhinitis during childhood, in order to find
preventive treatment measures.
Invited by FWF PhD Program W1213: Immunity in Cancer and Allergy (ICA)
(Coordinator: Josef Thalhamer)
- 17 -
Keynote Lecture
Abstract
C-type lectins in infection and immunity
Teunis Geijtenbeek
Department of Experimental Immunology, Academic Medical Center, Amsterdam, The
Netherlands. ([email protected])
Adaptive immune responses by dendritic cells (DCs) are controlled by pattern recognition
receptors such as Toll-like receptors (TLRs) and C-type lectins. Similarly, innate sensing by
these receptors is also involved in aberrant immune responses to allergens or pathogens.
Therefore, it is important to understand how pathogens/allergens are sensed by DCs and what
molecular mechanisms are triggered to initiate adaptive immunity. C-type lectins recognize
specific carbohydrate structures expressed by pathogens and allergens. Our studies have
shown that C-type lectins trigger signaling pathways that induce specific cytokines to dictate
T cell differentiation. Recently, we have shown that innate signaling by C-type lectin DCSIGN on DCs to fucose-expressing pathogens such as Schistosoma mansoni leads to the
induction of specific T helper (Th) type 2 and follicular Th differentiation. I will discuss the
molecular mechanisms involved in these processes. Furthermore, we have recently identified
an important role for C-type lectins in sensing of allergens and the induction of Th2 responses.
Thus, C-type lectins are crucial in tailoring immune responses to both pathogens and allergens,
and I will discuss the different mechanisms underlying these processes.
Invited by FWF PhD Program W1253: “Host response in opportunistic infections (HOROS)”
(Coordinator: Reinhard Würzner)
- 18 -
MeDALL: Mechanisms of the Development of ALLergy
Hopital de Villeneuve, University of Montpellier, Montpellier, France
Keynote Lecture
The origin of the epidemic of IgE-associated (allergic) diseases is unclear. MeDALL (Mechanisms of
the Development of ALLergy), an FP7 European Union project (No. 264357), aims to generate novel
knowledge on the mechanisms of initiation of allergy and to propose early diagnosis, prevention, and
targets for therapy. A novel phenotype definition and an integrative translational approach are needed to
understand how a network of molecular and environmental factors can lead to complex allergic diseases.
A novel, stepwise, large-scale, and integrative approach will be led by a network of complementary
experts in allergy, epidemiology, allergen biochemistry, immunology, molecular biology, epigenetics,
functional genomics, bioinformatics, computational and systems biology. The following steps are
proposed: (i) Identification of ‘classical’ and ‘novel’ phenotypes in existing birth cohorts; (ii) Building
discovery of the relevant mechanisms in IgE-associated allergic diseases in existing longitudinal birth
cohorts and Karelian children; (iii) Validation and redefinition of classical and novel phenotypes of IgEassociated allergic diseases; and (iv) Translational integration of systems biology outcomes into health
care, including societal aspects. MeDALL will lead to: (i) A better understanding of allergic phenotypes,
thus expanding current knowledge of the genomic and environmental determinants of allergic diseases
in an integrative way; (ii) Novel diagnostic tools for the early diagnosis of allergy, targets for the
development of novel treatment modalities, and prevention of allergic diseases; (iii) Improving the health
of European citizens as well as increasing the competitiveness and boosting the innovative capacity of
Europe, while addressing global health issues and ethical issues.
MeDALL follows over 44,000 children assessed from birth to 4 yrs (22,000), 8 yrs (19,000) and after
puberty (over 13,000) with a harmonized historical questionnaire for 199 questions using DataShaper.
MeDALL provides a harmonized MeDALL-Core Questionnaire (MeDALL-CQ) used retrospectively in
all cohorts and prospectively in 11 European birth cohorts. The harmonization of questions was
accomplished in 4 steps: (i) collection of variables from 14 birth cohorts, (ii) consensus on questionnaire
items, (iii) translation and back-translation of the harmonized English MeDALL-CQ into 8 other languages
and (iv) implementation of the harmonized follow-up. Three harmonized MeDALL-CQs (2 for parents of
children aged 4-9 and 14-18, 1 for adolescents aged 14-18) were developed.
Eczema, rhinitis, and asthma often coexist (comorbidity) in children, but the proportion of comorbidity
not attributable to either chance or the role of IgE sensitisation is unknown. We assessed these factors in
children aged 4-8 years in a prospective study study from 12 ongoing European birth cohort studies using
hypothesis-driven approaches. We assessed 16 147 children aged 4 years and 11 080 aged 8 years in
cross-sectional analyses. Coexistence of eczema, rhinitis, and asthma in the same child is more common
than expected by chance alone-both in the presence and absence of IgE sensitisation-suggesting that
these diseases share causal mechanisms. Although IgE sensitisation is independently associated with
excess comorbidity of eczema, rhinitis, and asthma, its presence accounted only for 38% of comorbidity,
suggesting that IgE sensitisation can no longer be considered the dominant causal mechanism of
comorbidity for these diseases. Similar results were observed using data-driven approaches and
unsupervised statistical analyses.
Allergy diagnosis based on purified allergen molecules provides detailed information regarding the
individual sensitization profile of allergic patients, allows monitoring of the development of allergic
disease and of the effect of therapies on the immune response to individual allergen molecules. Allergen
microarrays contain a large variety of allergen molecules and thus allow the simultaneous detection
of allergic patients’ antibody reactivity profiles towards each of the allergen molecules with only
minute amounts of serum. The MeDALL allergen-chip has been developed for the specific and sensitive
monitoring of IgE and IgG reactivity profiles towards more than 170 allergen molecules in sera collected
in birth cohorts.
Historical GWAS (23,000 children), prospective epigenetics (7,000), proteomics (1,000) and
transcriptomics (500) are currently been analysed.
Abstract
Jean Bousquet
Invited by FWF SFB F46: Towards prevention and therapy of allergy
(Coordinator: Rudolf Valenta)
- 19 -
Keynote Lecture
Abstract
Diversity of human memory subsets
Marginal zone B cells in humans: a distinct cell lineage
differing from IgM memory B cells.
Marc DESCATOIRE(1), Davide BAGNARA(1), Sandra WELLER(1), Deborah DUNN-WALTERS(2),
Jean-Claude WEILL(1) and Claude-Agnès REYNAUD(1)
(1) Institut Necker-Enfants-Malades (INEM) INSERM U1151, Faculté de Médecine Paris
Descartes, Site Broussais, Paris (France)
(2) Department of Immunobiology, King’s College London School of Medicine (UK)
In mice, marginal zone B cells (MZB) represent a distinct B cell lineage that arises in the
spleen where marginal zone precursor cells (MZP) differentiate under the control of the Notch2
pathway. In humans, the existence of such a lineage is still controversial. We proposed that,
in humans, blood IgM+IgD+CD27+ B cells represent circulating splenic MZB cells with a
differentiation pathway that could be conserved at least in part between mice and humans.
We identified in human spleen from young children a putative MZP subset, characterized
by its capacity to differentiate into MZB-like cells through Notch2 activation in vitro. It
accounts on average for 5% of total splenic B cells in children and decreases throughout
life. A transcriptomic analysis confirmed that MZP represent an intermediate differentiation
stage between naive and MZB cells. A Notch2 induction signature predominated among
genes discriminating MZP from naive B cells, a signature further developed among MZB
cells. Altogether, our results suggest that the early development of human blood and splenic
MZB cells, proceeds, as in the mouse, through a Notch2-dependent differentiation pathway,
and strengthen the proposition that IgM+IgD+CD27+ B cells differ from germinal centerdependent IgM memory B cells generated during T-dependent responses.
To further delineate MZ from IgM memory B cells, we performed high-throughput sequencing
of different splenic B cell subsets, using IgD and CD27 to define three different populations
with mutated Ig genes: IgD+CD27+ (“MZ”), IgD-CD27+ (“classical memory”, including cells
with IgG, IgA and IgM isotypes - the latter ones being named “IgM-only”) and IgD-CD27- cells
(double negative). We analyzed clones that share sequences between different subsets for
their mutation frequency distribution, their CDR3 length, their VH family and JH gene usage,
and compared these different characteristics with the bulk of sequences from their respective
subset of origin, for which these parameters constitute a distinct signature. Clonal relationships
between the IgM clones (originating from the MZ, M-only and double negative compartments)
show that all sequences involved display the characteristics of IgM-only B cells, whatever
their subset of origin. We therefore conclude that the clonal relationships shared between
the various IgM subsets do not represent filiation between them, but rather correspond to
a heterogeneous phenotype of the IgM-only population that concerns both IgD and CD27
expression, leading to a partial overlap with the MZ and double-negative gates. Clones shared
between the MZ and the switched IgG and IgA compartment also show, for their IgM part,
the mutation and repertoire characteristics of IgM-only cells and not of MZ B cells, reinforcing
the conclusion that IgM-only are true memory B cells, and constitute the only subset showing
precursor-product relationships with switched memory B cells.
This analysis thus reinforces the notion that IgM memory and marginal zone B cells represent
two different entities, with specific effector function in, respectively, T-dependent and
T-independent responses.
Invited by FWF PhD Program W1213: Immunity in Cancer and Allergy (ICA)
(Coordinator: Josef Thalhamer)
- 20 -
Stephen J. Galli
Departments of Pathology and of Immunology and Microbiology, Stanford University, Stanford,
California, USA. ([email protected])
Keynote Lecture
It is well known that mast cells (MCs) and IgE antibodies are important effector elements
in allergic disorders, and it is thought that they can contribute to host resistance to certain
parasites. However, it has been unclear whether MCs or IgE have any other beneficial
functions. In 1991, Margie Profet hypothesized that many allergens are derived from sources
(such as nuts, seafood, or venoms) which either might (e.g., foods) or always (e.g., venoms)
contain toxins (Profet, 1991). Profet also proposed that allergic reactions (manifested as
immediately occurring symptoms such as coughing or diarrhea) evolved to allow the sensitized
host to respond immediately to, and to neutralize and/or avoid, noxious substances which
might be indicative of potentially life-threatening situations. However, until recently, Profet’s
“toxin hypothesis” was largely ignored. In mammals, venoms provoke an innate inflammatory
response and pathology reflecting the activities of the contained toxins. Venoms also can
induce allergic sensitization and the development of specific IgE antibodies, which bind to
FcepsilonRI on tissue mast cells (MCs) and blood basophils, priming them to release mediators
of upon subsequent venom exposure. MCs also can be activated directly by certain venoms,
in the absence of specific IgE, and work in mice indicates that innate functions of MCs,
including degradation of venom toxins by MC-derived proteases, can enhance host resistance
to the venoms of certain arthropods (including the honeybee) and reptiles (Metz et al, 2006;
Schneider et al., 2007; Akahoshi, Song, et al., 2011). We found that mice injected with 1)
amounts of honeybee venom similar to what could be delivered in 1-2 stings, or 2) sublethal
amounts of Russell’s viper venom, developed specific Th2 responses which increased their
survival after subsequent challenge with potentially lethal amounts of the venom (Marichal,
Starkl et al., 2013). Our data indicate that IgE antibodies, FcepsilonRI, and FcepsilonRIalpha–
bearing effector cells (probably MCs) contribute to such acquired resistance to venom. The
evidence that IgE-dependent immune responses against venom can enhance survival in mice
supports the hypothesis that one important function of IgE is to help to protect the host
against noxious substances.
Abstract
Testing the toxin hypothesis of allergy: Roles of mast cells
and IgE in innate and acquired resistance to venoms
Acknowledgements
I thank all of the co-workers and collaborators who have contributed so importantly to the
work reviewed in my presentation, and the NIH, USA and the Department of Pathology,
Stanford University, for supporting of these studies.
Invited by FWF SFB F46: Towards prevention and therapy of allergy
(Coordinator: Rudolf Valenta)
- 21 -
Keynote Lecture
Abstract
Molecular functions and regulation circuits of
inflammatory cytokines
Alberto Mantovani
Humanitas Clinical and Research Center, University of Milan, 20089 Rozzano, Italy
Macrophages are key orchestrators of chronic inflammation. They respond to
microenvironmental signals with polarized genetic and functional programmes. M1
macrophages which are classically activated by microbial products and interferon-γ, are potent
effector cells which kill microorganisms and tumours . In contrast, M2 cells, tune inflammation
and adaptive immunity; promote cell proliferation by producing growth factors and products
of the arginase pathway (ornithine and polyamines); scavenge debris by expressing
scavenger receptors; promote angiogenesis, tissue remodeling and repair. M1 and M2 cells
represent simplified extremes of a continuum of functional states. Available information
suggests that TAM are a prototypic M2 population. M2 polarization of phagocytes sets these
cells in a tissue remodeling and repair mode and orchestrate the smouldering and polarized
chronic inflammation associated to established neoplasia. Intrinsic metabolic features and
orchestration of metabolism are key components of macrophage polarization and function.
Recent studies have begun to address the central issue of the relationship between genetic
events causing cancer and activation of protumour, smouldering, non resolving tumourpromoting inflammation. New vistas have emerged on molecules associated with M2 or M2like polarization and its orchestration in cancer. Recently, proof-of-principle has been obtained
that targeting TAM can be beneficial in human cancer.
References
Mantovani A, Allavena P, Sica A, Balkwill F Cancer-Related Inflammation. Nature 454: 436444, 2008.
Biswas S.K. and Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets:
cancer as paradigm. Nat Immunol 2010: 11, 889-896.
Sica A and Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J. Clin. Invest.
2012: 122, 787-795.
Biswas SK, Mantovani A. Orchestration of metabolism by macrophages. Cell Metab. 2012;
15(4): 432-7
Germano G, Frapolli R, Belgiovine C, et al. Role of macrophage targeting in the antitumor
activity of trabectedin. Cancer Cell 23: 249-262, 2013.
Jaillon S, Moalli F, Ragnarsdottir B, et al. The humoral pattern recognition molecule PTX3 is
a key component of innate immunity against urinary tract infection. Immunity 40: 621-632,
2014.
Invited by FWF PhD Program W1212: Inflammation and Immunity (IAI)
(Coordinator: Maria Sibilia)
- 22 -
Helminths and allergies: The IgE trick
(1)
(2)
(3)
(4)
(5)
Leiden University Medical Center, Leiden, The Netherlands
Noguchi Memorial Institute for Medical Research, Accra, Ghana
Hassanudin University, Makassar, Indonesia
University of Indonesia, Jakarta, Indonesia
Academic Medical Center, Amsterdam, The Netherlands
Closing
Keynote Lecture
Large geographical differences are seen in the prevalence of allergic disorders worldwide.
In affluent countries and in urban centers of low income countries, allergic disorders are a
serious problem whereas populations living in rural areas often appear to be protected. It
is interesting that helminth infections which are strong inducers of Th2 responses are highly
prevalent in rural areas of developing countries. This translates into high levels of total IgE
antibodies as well as allergen specific antibodies that do not seem to lead to allergic disorders.
There is evidence that IgE antibodies to helminthes can be cross reactive with allergens via
the carbohydrate structures. These cross reactive antibodies have poor biological activity. The
exact structures that the IgE antibodies are directed to are being studied in order to develop
strategies that might allow the induction of IgE with little biological activity in terms of inducing
basophil/mast cell degranulation. This might be an approach to prevent the development of
allergic disorders.
Abstract
Maria YAZDANBAKHSH (1), Abena AMOAH (1,2), Firdaus HAMID (1,3), Daniel BOAKYE (2),
Taniawati SUPALI (4), Ronald VAN REE (5)
Invited by FWF PhD Program W1248: Molecular, Cellular and Clinical Allergology (MCCA)
(Coordinator: Winfried F. Pickl)
- 23 -
Vortrag Klinischer
Allergietag
Abstract
Risiken der Allergiezunahme – Was wir aus den OstWest-Studien nach der deutschen Wiedervereinigung
gelernt haben
Johannes Ring, Ursula Krämer, Roma Schmitz, Heidrun Behrendt
Director emeritus Haut und Allergieklinik Biederstein, TU München
Der überraschende Befund von niedrigeren Heuschnupfen- und Asthmaprävalenzraten in Ostdeutschland
im Vergleich zu Westdeutschland zur Zeit des Mauerfalles und der deut-schen Wiedervereinigung gaben
Anlass zu verschiedenen epidemiologischen Studien, die sämtlich in der Folge einen steilen Anstieg
der Allergiehäufigkeit in Ostdeutschland zeigten. Nach ca. zehn Jahren hatten sich Ost und West in
Deutschland allergologisch weitgehend „harmonisiert“. Dieses Phänomen soll als Modell betrachtet
werden, um Ursachen für die „Allergie-Epidemie“ in der „westlichen“ Welt besser zu verstehen.
Tatsächlich wurde bislang nie untersucht, ob sich ein solches Muster auch in allen vergleichenden Studien
und für alle Manifestationen allergischer Erkrankungen nachweisen ließ. Es erscheint interessant, aus
diesem „Experimentum dictaturae“ zu lernen, wodurch ein Volk in einem Land mit ähnlicher Ethnik, Kultur
und klimatischer Kondition lediglich durch einen politisch bedingten unter-schiedlichen Lebensstil getrennt
war,.
Insgesamt 14 Querschnittsstudien wurden einer Metaanalyse unterzogen, und die Verände-rungen der
Ost-West-Verhältniszahlen in der Dekade nach der deutschen Wiedervereinigung verglichen.
Heuschnupfen als die typischste atopische Erkrankung zeigte die klarsten Unterschiede zur Zeit der
Wiedervereinigung zwischen Ost- und Westdeutschland und die deutlichsten Kon-vergenzraten.
Es fand sich ein deutlicher Unterschied zwischen allergischen Atemwegserkrankungen (Heu-schnupfen,
Asthma) und Hautmanifestation als atopisches Ekzem, welches in Ostdeutsch-land zur Zeit der
Wiedervereinigung gleich häufig oder häufiger war, als die Atemwegsaller-gien.
Die Risikofaktoren für Atemwegsallergien (Ozon, Feinstaub, Verkehrsbelastung) unterschei-den sich
deutlich von den klassischen Risikofaktoren für andere Atemwegserkrankungen wie z. B. Bronchitis
(Schwefeldioxid, grober Schwebstaub, industrieller Smog). Häufig diskutierte Innenraumfaktoren
wie Teppichboden, Bettzeug oder Haustierhaltung konnten für den An-stieg der Allergieprävalenz in
Ostdeutschland nicht verantwortlich gemacht werden. Aller-dings fand sich als möglicher Faktor, der in
allen Studien präsent war, Einzelraumheizung mit fossilen Brennstoffen sowie Krippenbesuch bzw. das
Leben in einer Familie mit Geschwistern als Allergie-protektiv. Nicht in allen Studien untersucht, aber
dennoch von Interesse: Wurm-infektionen schienen protektiv für Atemwegsallergien aber eher fördernd
für atopisches Ekzem zu sein. In einer Studie fand sich ein protektiver Effekt der Keuchhustenimpfung,
wel-che in Ostdeutschland vor der Wiedervereinigung in nahezu 100 % durchgeführt wurde, im Vergleich
dazu nur bei 75 % der westdeutschen Kinder.
Die West-Ost-Unterschiede verschwanden bei Kindern, die nach der Wiedervereinigung ge-boren wurden,
relativ schnell, blieben jedoch bei Erwachsenen-Studien noch länger erhalten.
Die gefundenen Auffälligkeiten stellen möglicherweise nur Marker von noch genauer zu identifizierenden
Kausalfaktoren dar.
Literatur:
Krämer U, Schmitz R, Ring J, Behrendt H. What can reunification of East and West Germany tell us about
the cause of the allergy epidemic? Clin Exp Allergy, in press
Eingeladen von: Schwerpunkt Biowissenschaften und Gesundheit der Universität Salzburg
(Koordinator: Josef Thalhamer)
- 24 -
Knut BROCKOW
Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität
München, Biedersteiner Straße 29, 80802 München ([email protected])
Vortrag Klinischer
Allergietag
Die häufigsten Auslöser von Arzneimittel-Unverträglichkeitsreaktionen sind möglicherweise
Analgetika. Es wird eine durch Zyklooxygenasehemmung bedingte Reduktion von protektiven
Prostaglandinen bzw. Vermehrung von Lipoxygenasestoffwechselprodukten angenommen.
Bis zur allergologischen Klärung sollten alle in Frage kommenden Auslöser gemieden
werden. Die allergologische Diagnostik von Überempfindlichkeitsreaktionen auf Arzneimittel
wird in einer deutschsprachigen Leitlinie überarbeitet; daneben existieren Europäische
Leitlinien. Alle empfehlen die Austestung betroffener Patienten zur Verhinderung erneuter
Reaktionen. Zumeist werden die Auslöser einer Analgetika-Überempfindlichkeit durch
Anamnese, Hauttest und In-vitro-Untersuchungen nicht sicher identifiziert, insofern sind
zur Klärung Provokationstestungen notwendig. Diese Praxis wird oft nicht befolgt, da die
personellen und methodischen Kapazitäten fehlen. Die allergologische Versorgung, ist
anhand der DRGs nicht kostendeckend. Es gibt zu wenige allergologische Zentren, die bis
zur Provokationstestung diagnostizieren. In dieser Siuation müssen häufig Kompromisse
eingegangen werden. Bei mindestens dreimaliger Urtikaria nach Analgetikaeinnahme war
die Wahrscheinlichkeit einer erneuten Reaktion > 95%. Bei eindeutigen Reaktionen sollte
eine Austestung von Alternativanalgetika erfolgen, da hohe Kreuzreaktivitäten zwischen
Cox1-hemmenden Analgetika bestehen. Cox2-Hemmer, wie Celecoxib werden von >95%
aller Patienten vertragen, ebenso Opiatanalgetika und Paracetamol zumeist in niederigen
Dosierungen ≤500mg. Das Risiko-/Nutzenverhältnis einer stationären Provokation mit diesen
Ausweichanalgetika kann diskutiert werden.
Abstract
Analgetikaintoleranz- braucht wirklich jeder Patient
einen Provokationstest?
- 25 -
Vortrag Klinischer
Allergietag
Abstract
Volkskrankheit Anaphylaxie - werden unsere
Patienten ausreichend versorgt?
Margitta WORM
Allergie-Centrum-Charité, Klinik für Dermatologie, Venerologie und Allergologie,
Charité Universitätsmedizin Berlin
Die Anaphylaxie ist definiert als eine sich rasch entwickelnde Multiorganerkrankung, die
potentiell tödlich verlaufen kann. Nahrungsmittel, Insektengifte und Medikamente sind die
häufigsten Auslöser. Versorgungsaspekte der Anaphylaxie betreffen sowohl die Diagnostik
als auch die Therapie, wobei hier das Akut- aber auch das Langzeitmanagement
berücksichtigt werden müssen. Zur Diagnostik der Anaphylaxie allgemein muss aus
versorgungsmedizinischer Sicht festgestellt werden, dass bestimmte Patientengruppen ein
allergologisches Zentrum zur diagnostischen Abklärung gar nicht erreichen. Eine
Verbesserung wäre hier durch eine Vernetzung von notärztlichen Zentren mit
allergologischen Zentren zu erzielen.
Die Akuttherapie anaphylaktischer Reaktionen umfasst die i.m. Applikation von Adrenalin mit
Hilfe eines Autoinjektors sowie Antihistaminika und Kortikosteroide. Das einzige Medikament,
welches direkt den Symptomen einer schweren Anaphylaxie entgegenwirkt, ist Adrenalin.
Daher wird es in allen derzeit verfügbaren nationalen und internationalen Leitlinien als
Medikament der ersten Wahl empfohlen. Die Daten aus dem Anaphylaxie Register, wo
Patienten mit schweren allergischen Reaktionen von allergologischen Zentren gemeldet
werden, zeigen jedoch, dass nur weniger als 20% der Patienten tatsächlich trotz des
Vorliegens einer schweren Reaktion mit Herzkreislauf- und/oder Lungenbeteiligung
Adrenalin erhalten. Eine detaillierte Analyse der Versorgung von Patienten nach
Schweregrad ergibt, dass zwar Adrenalin bei Patienten in der allergischen Schocksituation
häufiger gegeben wird, jedoch der Einsatz beispielsweise in der Gruppe der Patienten mit
respiratorischen Symptomen und Hautsymptomen deutlich weniger häufig ist. Somit zeigen
die Daten aus dem Anaphylaxie Register, dass die Akutversorgung der Patienten verbessert
werden muss. Dies kann durch verbesserte Aufklärungsmaßnahmen nicht nur für Patienten,
sondern auch dem ärztlichen Personal erzielt werden. Weitere Studien, die belegen, dass
eine frühzeitige Gabe von Adrenalin das Überleben und den Verlauf einer schweren
allergischen Reaktion verbessern kann, können dazu beitragen, dieses Ziel zu erreichen.
Key words: Anaphylaxie, Notfallversorgung, Adrenalin
Referenzen:
Worm M, Moneret-Vautrin A, Scherer K, Lang R, Fernandez-Rivas M, Cardona V, Kowalski ML,
Jutel M, Poziomkowska-Gesicka I, Papadopoulos NG, Beyer K, Mustakov T, Christoff G, Bilò MB,
Muraro A, Hourihane JO, Grabenhenrich LB. First European data from the network of severe
allergic reactions (NORA). Allergy. 2014 Oct;69(10):1397-404.
Worm M, Eckermann O, Dölle S, Aberer W, Beyer K, Hawranek T, Hompes S, Koehli A, Mahler
V, Nemat K, Niggemann B, Pföhler C, Rabe U, Reissig A, Rietschel E, Scherer K, Treudler R,
Ruëff F.
Triggers and treatment of anaphylaxis: an analysis of 4,000 cases from Germany, Austria and
Switzerland. Dtsch Arztebl Int. 2014 May 23;111(21):367-75.
Grabenhenrich L, Hompes S, Gough H, Ruëff F, Scherer K, Pföhler C, Treudler R, Mahler V,
Hawranek T, Nemat K, Koehli A, Keil T, Worm M. Implementation of anaphylaxis management
guidelines: a register-based study. PLoS One. 2012;7(5):e35778.
- 26 -
Wie evident ist die Rekombinanten-basierte Diagnostik in der Praxis?
Jörg KLEINE-TEBBE, Juliane ACKERMANN-SIMON, Gerald HANF
Abstract
Molekulare Allergologie in der Praxis: Zwischen
Evidenz und anekdotischer Erfahrung
Allergie- u. Asthma-Zentrum Westend, Praxis Hanf, Ackermann & Kleine-Tebbe, Berlin
Warum besitzt die Molekulare Allergiediagnostik Vorteile?
Folgende Gründe sprechen für den Einsatz von Einzelallergenen:
1. Erhöhte Testempfindlichkeit (analytische Sensitivität), besonders bei
unterrepräsentierten oder fehlenden wichtigen Allergenen im Extrakt (Beispiele in Tab, 1,
mittlere Spalte)
2. Verbesserte Testselektivität (analytische Spezifität/Selektivität), besonders wenn
das selektierte IgE-Repertoire gegen ein Allergen zusätzliche Aussagen zum potentiellen
Risiko (Beispiele in Tab. 1, rechte Spalte), zur primären (genuinen) Sensibilisierung oder zur
möglichen Kreuzreaktivität gestattet (Beispiele in Tab. 2, rechte Spalten).
Tab. 1
Beispiele
Höhere analytische
(Allergenquellen) Sensitivität
Erdnuss
Ara h 10, Ara h 11 (Oleosine)
Soja
Gly m 4
Haselnuss
Cor a 1 (Bet v 1-homolog)
Weizen
Fleisch
Bienengift
Wespengift
Tri a 19 (Omega-5-Gliadin)
alpha-GAL
Ves v 5
Vortrag Klinischer
Allergietag
Allergenmoleküle (meist Proteine, seltener Kohlehydratepitope) eröffnen neue Möglichkeiten
für die allergenspezifische Immunglobulin E (IgE)-Diagnostik.
Größere analytische
Spezifität/Selektivität
Ara h 1, (7S-Globulin)
Ara h 2 (2S-Albumin)
Ara h 3, (11S-Globulin)
Ara h 9 (LTP, Mittelmeerraum)
Glym 5
Gly m 6
Cor a 14 (2S-Albumin),
Cor a 9 (11S-Globulin)
Cor a 8 (LTP, Mittelmeerraum)
alpha-GAL
Api m 1
Ves v 1, Ves v 5
Tab. 2
Fortsetzung siehe S. 28f
- 27 -
Weizen
Fleisch
Bienengift
Wespengift
Tri a 19 (Omega-5-Gliadin)
alpha-GAL
Ves v 5
Cor a 9 (11S-Globulin)
Cor a 8 (LTP, Mittelmeerraum)
alpha-GAL
Api m 1
Ves v 1, Ves v 5
Tab. 2
Pflanzenfamilien u. spezies
Relevante Pollenpflanzen
für Allergiesymptome in
Deutschland
Birkengewächse (Hasel,
Erle, Birke, Hainbuche)
u. Buchengewächse
(Buche, Eiche)
Ölbaumgewächse
(Esche, Ölbaum)
Süßgräser (incl. Roggen)
Beifuß
Ambrosia (Traubenkraut,
Ragweed)
Major-Allergene
aus diversen
Proteinfamilien
Minor-Allergene
(Pollen-Panallergene)
Profiline
Polcalcine
Bet v 1
Bet v 2
Bet v 4
Ole e 1
Ole e 2
Ole e 3
Phl p 1, Phl p 5
Phl p 12
Phl p 7
Art v 1
Amb a 1
Art v 4
Amb a 8
Art v 5
Amb a 10
Zur Labordiagnostik bereits verfügbare Einzelallergene (fett gedruckt): Markerallergene
(mittlere. Spalte) zur IgE-Diagnostik als Zeichen einer primären Sensibilisierung und
Pollen-Panallergene (re. Spalten) als Hinweis auf und Basis für klinisch fraglich relevante
Kreuzreaktionen zwischen sämtlichen Pollen(extrakt)spezies.
Wann kommt die Molekulare Allergiediagnostik in Frage?
Die richtige Indikation für den Einsatz von Einzelallergenen lässt sich nur
3. individuell (abhängig vom klinischen Kontext/Vorgeschichte) und
4. allergenspezifisch (abhängig von Allergenquelle und verfügbaren Einzelallergenen)
und nicht pauschal begründen.
Wie wird die Molekulare Allergiediagnostik sinnvoll eingesetzt?
Folgende Beispiele bei Verdacht auf Nahrungsmittelallergie (NMA), Insektengiftallergie
oder Sensibilisierung gegen Pollen-Panallergene illustrieren in Tab. 3 den Einsatz von
Einzelallergenen zur allergenspezifischen IgE-Diagnostik.
- 28 -
Tab. 3
Klinisches Bild
Anaphylaxie nach
Anstrengungen und Mahlzeit
mit Weizenprodukt(en)
"Katzen-SchweinefleischSyndrom"
verzögerte Fleisch-Allergie
(z.B. Urtikaria)
Allergie z.B. auf Weintrauben,
Heidelbeeren, Zitrusfrüchte
Orales Allergie-Syndrom
(OAS) häufig auf Nüsse, Kernund Steinobst etc., ggf.
systemische Reaktionen auf
Soja (nativ)
OAS nach ungewöhnlichen
pflanzlichen Nahrungsmitteln
(Melone, Exoten wie Litschi,
Zitrusfrüchte)
Doppelsensibilisierung gegen
Bienen- und Wespengift
Multiple Sensibilisierungen
gegen Pollenextrakte (Baum-,
Gräser- u. Kräuterpollen)
fraglicher Relevanz
Allergologische
Verdachtsdiagnose
Anstrengungsabhängige
Weizenallergie
Einzelallergene zur IgEDiagnostik
Tri a 19 (Omega-5 Gliadin)
Allergie gegen tierische
Serumalbumine
Sensibilisierung gegen Į-GAL
Fel d 2 oder Bos d 6
Sensibilisierung gegen LipidTransferproteine (LTP)
Sensibilisierung gegen Bet v 1Homologe (PR 10 Proteine)
Pru p 3 (Pfirsich-LTP)
Sensibilisierung gegen
Profiline
Pru p 4 (oder Bet v 4, Phl p
12, Hev b 8)
Serologische Kreuzreaktion
durch gemeinsame Allergene
in Bienen- u. Wespengift
Serologische Kreuzreaktion
durch Pollen-Panallergene
(Profilin u./o. Polcalcin)
Api m 1
Ves v 1
Ves v 5
Bet v 2 oder Phl p 12 (Profilin)
Bet v 4 oder Phl p 7
(Polcalcin)
Į-GAL (Thyreoglobulin)
Bet v 1 und ggfs. Gly m 4 (Bet
v 1-homolog)
5. Zur individuellen Vorhersage der klinischen Relevanz einer Sensibilisierung ist das IgE gegen
Allergenmoleküle (z.B. ImmunoCAP, ThermoFisher, Freiburg) nur bedingt geeignet, da es
sich um einen Sensibilisierungstest handelt. Bei Nahrungsmittelallergie lässt sich bestenfalls
ein relatives Risiko aufgrund des IgE-Profils ermitteln, aber keine sichere Vorhersage zur
(zukünftigen) Verträglichkeit treffen.
6. Die klinische Relevanz sämtlicher IgE-Befunde ist nur bei korrespondierenden Symptomen
gegeben und muss individuell geprüft werden (Vorgeschichte, Symptomprotokoll, ggfs.
Provokation mit der zugehörigen Allergenquelle). Somit ermittelt der behandelnde Arzt auch
bei Verwendung von Einzelallergenen die klinische Relevanz der diagnostischen Ergebnisse,
nicht der Test.
Weiterführende Literatur
Canonica GW, Ansotegui IJ, Pawankar R, Schmid-Grendelmeier P, van Hage M, BaenaCagnani CE, et al. A WAO - ARIA - GA(2)LEN consensus document on molecular-based allergy
diagnostics. The World Allergy Organization journal. 2013;6(1):17. PubMed PMID: 24090398.
Pubmed Central PMCID: 3874689 (Open Access).
Kleine-Tebbe J, Jappe U. Molekulare Allergiediagnostik: Entwicklung und die Bedeutung für die
klinische Praxis. Allergologie. 2013;36:327-49.
Kleine-Tebbe J, Jappe U. Molekulare Allergologie (Taschenbuch). Dustri-Verlag Dr. Karl Feistle,
München-Deisenhofen 2014, ISBN 978-3-87185-491-0
- 29 -
Oral Presentation
Abstract 1
Engineering hypoallergenic variants of the peanut
allergens Ara h 2 and Ara h 6
Thomas EIWEGGER (1)*, Merima BUBLIN(2)*, Klara SCHMIDTHALER(1), Maria
KOSTADINOVA(2), Christian RADAUER(2), Christine HAFNER(3), Zsolt SZÉPFALUSI(1), EvaMaria VARGA(4), Heimo BREITENEDER(2) *contributed equally
(1) Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna,
Austria
(2) Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna,
Austria
(3) Karl Landsteiner Institute for Dermatological Research, St. Poelten, Austria
(4) Department of Paediatrics, Respiratory and Allergic Disease Division, Medical University
Graz, Austria
Background: Currently no allergen specific immunotherapy (IT) for peanut allergic individuals
is available due to side effects. Modified allergens with a highly reduced IgE-binding capacity
with preserved T cell epitopes are needed for IT.
Aim: We aimed to generate modified major peanut allergens Ara h 2 and Ara h 6 with reduced
IgE binding, preserved T-cell epitopes and intact tertiary structure for treatment of peanut
allergy.
Methods: The hypoallergens were engineered by swapping of neighbouring segments of
5-10 amino acids residues in surface exposed loops. Ara h 2 and Ara h 6 were purified from
commercial roasted peanuts, and mutated Ara h 2 and Ara h 6 were produced in E. coli SHuffle
T7 cells. IgE-binding (ELISA, Immunoblot), IgE cross-linking capacity (Basophil Activation
Test), T-cell stimulatory capacity (3H-Thymidine incorporation assay, intracellular cytokine
staining, multiplex ELISA) and whole mRNA expression in allergen specific T-cells were
evaluated.
Results: Mutated Ara h 2 and Ara h 6 were fully capable in inducing allergen specific T-cell
proliferation with mildly reduced Th2 cytokine induction. Basophil activation was reduced by
90-97%. Allergen specific T-cell gene array revealed minimal changes in the T-cell mRNA
signature suggestive for keeping relevant T-cell epitopes and response mechanisms intact.
Conclusions: Hypoallergenic peanut variants with significantly reduced IgE binding but intact
T-cell activation may be an option for allergen-specific IT.
Acknowledgements
This work was funded by BRIDGE Grant 820127 from the Austrian Research Promotion Agency
(FFG) and the Medical Scientific fund of the Mayor of the city of Vienna (no. 11013) and the
SFP and PhD Program Molecular, Cellular and Clinical Allergy, MCCA (no w1248-B13)
Contact / E-Mail:
[email protected]
- 30 -
Heidi A. Müller(1) , Luis. F. Pacios(2), Cristina Gomez-Casado(2), G. HofstetteR(1),
Georg A. Roth(3), Josef Singer(4), Araceli Diaz-Perales(2), Erika Jensen-Jarolim(1,4),
F. Roth-Walter(1)
Background: The major cow milk allergen Bos d 5 belongs to the lipocalin-family and as such
is a promiscuous ligand transporter. In this study we investigated its ability to bind to ironsiderophore complexes and tested for immune-modulatory consequences.
Oral Presentation
(1) Comparative Medicine, Messerli Research Institute of the University of Veterinary Medicine
Vienna, Medical University Vienna and University Vienna, Vienna, Austria
(2) Biotechnology Department, Center for Plant Biotechnology and Genomics, Technical
University of Madrid, Madrid, Spain
(3) Department of Anesthesiology, General Intensive Care and Pain Medicine, Medical
University of Vienna, Austria
(4) Comparative Immunology and Oncology, Department of Pathophysiology and Allergy
Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of
Vienna, Vienna, Austria
Abstract 2
The major cow milk allergen, Bos d 5, is able to bind
siderophore bound iron and influences T-helper cells
according to its binding state
Methods: Docking to Bos d 5 of catechol-based flavonoids (quercetin, myricetin, luteolin)
selected as siderophores were performed using AutoDock Vina. Prussian blue staining of Bos d
5 carrying iron (holo-) or not (apo-form) were performed. Peripheral blood mononuclear cells
(PBMCs) of 25 human subjects were activated and stimulated for 18h with apo- or holo-form.
Subsequently, cells and supernatants were analysed by flow cytometry and their cytokinecontent.
Results: Docking analysis of Bos d 5 revealed that it is able to bind iron via catechol-based
flavonoids that act as siderophores. When incubated with PBMCs, only the apo-form led to an
increase of CD4+positive cells and significantly elevated IL13 and IFNγ-levels. In contrast,
holo-form decreased numbers of CD4 expressing cells and induced apoptosis.
Conclusion: Our data give evidence that Bos d 5 is capable of binding iron via siderophores.
The apo-form promotes Th2 cells and inflammation, whereas the holo-form appears to be
immunosuppressive.
Acknowledgements
This work was supported by the F4606-B19 of the Austrian Science Fund FWF. J. Singer was
financially supported by CCHD W1205-B09 of the Austrian Science Fund, FWF. C. GomezCasado was financially supported with the grant BES-2010-034628of the FPI Programme from
the Spanish Government (MICINN/MINECO).
Contact / E-Mail:
[email protected]
- 31 -
Oral Presentation
Abstract 3
Why I? IgE profiling and lifestyle analysis of 501
Austrian school children
Teresa STEMESEDER(1), Eva KLINGLMAYR(1), Bettina SCHWEIDLER(1), Lisa
LUEFTENEGGER(2,3), Stephanie MOSER(4), Roland LANG(3), Martin HIMLY(1), Gertie J.
OOSTINGH(2), Arne BATHKE(5), Joerg ZUMBACH(4), Thomas HAWRANEK(3), Gabriele
GADERMAIER(1)
(1)
(2)
(3)
(4)
(5)
University of Salzburg, Department of Molecular Biology, Salzburg, Austria
Salzburg University of Applied Sciences, Biomedical Sciences, Salzburg, Austria
Paracelsus Medical University Salzburg, Department of Dermatology, Salzburg, Austria
University of Salzburg, School of Education, Salzburg, Austria
University of Salzburg, Department of Mathematics, Salzburg, Austria
This study aims to clarify reasons for the increasing numbers of patients suffering from allergic
diseases by analyzing the IgE sensitization profiles and lifestyle of 501 Austrian school children
aged 13-21 from different geographical regions.
Capillary blood samples were obtained from all participants and analyzed using the
ImmunoCAP ISAC. Demographic data, self-reported health status including allergies and other
lifestyle conditions such as smoking and diet were surveyed in a questionnaire.
Forty percent of subjects declared to suffer from allergies including self-reported adverse
reactions. IgE-reactivity to any of the 112 molecules on the ISAC chip was observed in 53% of
subjects. Highest sensitizations to inhalant allergens were found to grass pollen (36%), tree
pollen (28%) and house dust mites (23%). No difference in overall IgE sensitization was found
between alpine, urban and rural living areas whereas the sensitization rate to house dust mite
was significantly higher in urban regions. Among smokers the sensitization rate of 76% was
found to be significantly higher.
Investigations of allergic and non-allergic subjects showed a very high sensitization rate and
might allow identification of factors influencing the development of allergic diseases.
Acknowledgements
The study was funded by Sparkling Science, a program of the Federal Ministry of Science,
Research and Economy, Vienna, Austria.
Contact / E-Mail:
[email protected]
- 32 -
Eva WOLLMANN(1), Carl HAMSTEN Carl(2,3), Elopy SIBANDA(4), Mary OCHOME(1),
Margarethe FOCKE-TEJKL(1), Anna ASARNOJ(2,5), Annika ÖNELL(6), Gunnar LILJA(7), Daniela
GALLERANO(1), Christian LUPINEK(1), Theresa THALHAMER(8), Richard WEISS(8), Josef
THALHAMER(8), Magnus WICKMAN(7,9), Rudolf VALENTA(1), Marianne VAN HAGE(2)
Peanut allergy may cause life-threatening allergic reactions. Here we investigated
immunological patterns of clinical tolerance to peanut in peanut sensitized but asymptomatic
patients from central Africa compared to Swedish peanut allergic vs. sensitized but
asymptomatic patients.
Sera from allergic patients (n=54) from Zimbabwe with IgE to peanut but without symptoms,
and sera from peanut allergic (n=25) and sensitized but asymptomatic (n=25) patients from
Sweden, were analyzed for total IgE and IgE, IgG and IgG4 reactivity towards Ara h 1-3, 6,
8, 9 using an allergen microarray. Allergenic activity was investigated by basophil activation
assays. IgE to Ara h 2 peptide epitopes was analyzed.
Fourty-six percent of the African and all peanut allergic Swedish patients showed IgE towards
one of the highly allergenic peanut allergens (Ara h 1-3, 6, 9). However, 48% of the African
patients had IgE to cross-reacting carbohydrates (CCD) with low allergenic activity and 60% of
the Swedish asymptomatic patients had IgE against the PR-protein Ara h 8. Peanut IgE from
both peanut asymptomatic patients groups showed very poor allergenic activity compared to
IgE from peanut allergic patients. Asymptomatic patients almost completely lacked IgE to Ara
h 2 peptide epitopes which were recognized by peanut allergic patients.
Natural clinical tolerance to peanut in the African and Swedish patients could be explained by
exclusive IgE to low allergenic peanut components e.g. such as profilins, CCD and/or PR-10
proteins and by poor allergenic activity of peanut-specific IgE.
Oral Presentation
(1) Institute for Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology
and Immunology, Medical University of Vienna
(2) Department of Medicine Solna, Clinical Immunology and Allergy Unit, Karolinska Institutet,
and University Hospital, Stockholm, Sweden
(3) Center for Inflammatory Diseases, Karolinska Institutet, Stockholm, Sweden
(4) University of Zimbabwe Medical School, Harare, Zimbabwe
(5) Astrid Lindgren Children’s Hospital, Stockholm, Sweden
(6) Thermofisher Scientific ImmunoDiagnostics, R&D, Uppsala Sweden
(7) Department of Pediatrics, Sachs’ Children’s Hospital, Stockholm, Sweden
(8) Department of Molecular Biology, University of Salzburg and
(9) Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Abstract 4
Natural clinical tolerance to peanut in African
patients is caused by poor allergenic activity of
peanut IgE
Acknowledgements
Supported by the FWF-funded doctoral program IAI and SFB F46, the Swedish Research
Council, the Stockholm County Council, the Swedish Heart-Lung Foundation, the Center for
Inflammatory Diseases Karolinska Institutet, the Swedish Asthma and Allergy Association’s
Research Foundation, the Swedish Cancer and Allergy Foundation, Konsul Th Bergs Foundation,
the King Gustaf V 80th Birthday Foundation, the Hesselman Foundation, the Magnus Bergvall
Foundation, Karolinska Institutet and the FP7-funded program MeDALL of the European Union.
Contact / E-Mail:
[email protected]
- 33 -
Oral Presentation
Abstract 5
Differences in molecular sensitization profiles
towards animal allergens revealed by allergen microarray in two generation of patients with respiratory
allergy
Victoriya GARIB, Eva WOLLMANN, Rudolf VALENTA
Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center of
Pathophysiology, Infectiology and Immunology, Medical University of Vienna
Background: The prevalence of allergic diseases has increased significantly over the past
several decades. The exposure to animal allergens and IgE-sensitization to domestic inhalant
allergens is a major risk factor for asthma.
Objective: The aim of this study was to determine the IgE-sensitization profiles towards animal
allergens in 2 generations of patients with respiratory allergy and their co-sensitizations with
pollen allergens.
Methods: Sera of 50 adult patients with allergic rhinitis and/or bronchial asthma (young adults;
20-29 years, n=20 and middle aged adults; 30-49 years, n=30) were analyzed using an
allergen micro-array containing 112 different allergen molecules (ImmunoCAP ISAC; Thermo
Scientific). All patients are native Uzbek from Tashkent metropolis.
Results: Significant differences were found in the IgE sensitization patterns in the 2 groups:
young patients show higher IgE sensitization rates towards animal allergens (75%) as
compared to the elder group (30%).
An increase of IgE reactivity from 23% in the middle-aged adults to 61% in younger patients
against the uteroglobin rFel d 1 could be detected and mean rFel d 1 specific IgE ISU levels
raised from 2.1 to 38.5. The younger generation also displayed specific IgE for the lipocalins
rCan f 1, rFel d 4, and nMus m 1, and to the dog prostatic kallikrein rCan f 5, whereas no
reactivity against rCan f 2 and rEqu c 1 was detectable. Also in this group IgE sensitization to
animal serum albumins (nCan f 3, nEqu c 3, and nFel d 2) could be found. High co-sensitization
rates to animal and the grass pollen allergens nCyn d 1 and rPhl p 1 were observed in the
young group vs. more frequent co-sensitizations against animal and the weed pollen allergen
nSal k 1 in the middle aged adults group.
Significant differences were also found in the IgE sensitization patterns between the clinical
groups: patients with bronchial asthma were more frequently co-sensitized to cat and dog
allergens or cat and house dust mite allergens (28% vs. 10%, and 18% vs. 0% respectively)
and showed higher mean IgE levels towards rFel d 1 (31.1 vs. 21.1 ISU-E) compared to the
group with allergic rhinitis.
Conclusion: In the young generation of patients with respiratory allergy higher rates of IgE
sensitizations towards animal allergens were found compared to the elder patient group, most
prevalent was the major cat allergen rFel d 1. Occurrence of IgE co-sensitization to unrelated
allergens may increase the risk of asthma development and progression.
Acknowledgements
This study was supported by the Austrian Science Fund (FWF) and was performed in the
framework of International Network of Universities for Molecular Allergology and Immunology.
Contact / E-Mail:
[email protected]
- 34 -
Christina BANNERT(1), Zsolt SZÉPFALUSI(1), Leila RONCERAY(1), Elisabeth MAYER(1),
Michaela HASSLER(1), Eva WISSMANN(1), Eleonora DEHLINK(1), Saskia GRUBER(1),
Alexandra GRAF(2), Christian LUPINEK(3), Rudolf VALENTA(3), Thomas EIWEGGER(1),
Radvan URBANEK(1)
(1) Department of Pediatrics, Medical University of Vienna, Austria
(2) Center for Medical Statistics, Informatics and Intelligent Systems, Medical University of
Vienna, Austria
(3) Department of Pathophysiology and Allergy Research, Medical University of Vienna
Oral Presentation
Prevention of IgE sensitizations by allergen-specific immunotherapy has been described.
Prospective data using a preventive approach in children is missing. We initiated a prospective
pilot study investigating the safety, immunomodulatory and sensitization-preventive effect of
sublingual immunotherapy (SLIT) in sensitized, clinically asymptomatic 2-5 year old children.
In this double-blind, randomized, placebo-controlled study 31 mono/oligo-sensitized children
to house dust mite or grass pollen were included. SLIT with the respective source (n=15)
or placebo (n=16) was applied for 2 years. Skin prick testing and specific IgE and IgG
measurements were recorded at baseline, 12 and 24 months. At the same time allergenspecific proliferation and Treg function was measured.
Preventive SLIT in young children was safe. After 12 and 24 months of treatment the rate of
allergen-specific sensitization was comparable in the verum and the placebo group. However,
verum-treated patients displayed an up-regulation of allergen-specific IgG (p<0.05). IL10dependent inhibition (p<0.05) was observed in vitro in the treatment group but not in the
placebo group.
We conclude that preventive SLIT is safe in 2-5 year old children and induces regulatory
mechanisms involving allergen-specific IgG and IL10.
Abstract 6
Preventive sublingual immunotherapy in preschool
children: first evidence for safety and pro-tolerogenic
effects
Contact / E-Mail:
[email protected]
- 35 -
Oral Presentation
Abstract 7
Jagunal-homolog 1 is a critical regulator of
neutrophil function in fungal host defense
Gerald WIRNSBERGER(1), Florian ZWOLANEK(2), Johannes STADLMANN(1,3), Luigi
TORTOLA(1), Shang Wan LIU(1), Thomas PERLOT(1), Päivi JAERVINNEN(4), Gerhard
DUERNBERGER(1,3), Ivona KOZIERADZKI(1), Renu SARAO(1), Alba DE MARTINO(5), Kaan
BOZTUG(6,7), Karl MECHTLER(1,3), Karl KUCHLER(2), Christoph KLEIN(4), Ulrich ELLING(1)
and Josef M. PENNINGER(1)
(1) IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030
Vienna, Austria
(2) Medical University of Vienna, Max F. Perutz Laboratories, Department of Medical
Biochemistry, 1030 Vienna, Austria
(3) IMP, Institute for Molecular Pathology, 1030, Vienna, Austria
(4) Department of Pediatrics, Dr. Von Hauner Children’s Hospital, Ludwig-Maximilians
University, Munich, Germany
(5) CSF, Campus Science Support Facility, 1030 Vienna, Austria.
(6) CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna,
Austria
(7) Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria
Neutrophils are key innate immune effector cells essential to fight bacterial and fungal
pathogens. Here we report that mice carrying a hematopoietic lineage-specific deletion of
Jagunal homolog 1 (Jagn1) cannot mount an efficient neutrophil-dependent immune response
to the human fungal pathogen Candida albicans. Global glycobiome analysis revealed marked
alterations in the glycosylation of proteins involved in cell adhesion and cytotoxicity of Jagn1deficient neutrophils. Functional analysis confirmed marked defects in neutrophil migration in
response to Candida albicans infection, impaired formation of cytotoxic granules, as well as
defective MPO-release and killing of Candida albicans. GM-CSF treatment protected mutant
mice from increased weight loss and accelerated mortality after Candida albicans challenge.
Importantly, GM-CSF also restored the defective fungicidal activity of bone marrow cells from
patients with JAGN1 mutations. These data directly identify Jagn1/JAGN1 as a novel regulator
of neutrophil function in microbial pathogenesis and uncover a potential treatment option for
human patients.
Acknowledgements
We thank all members of the Penninger laboratory for helpful discussions and technical
support. We thank all members of the IMP-IMBA Biooptics service facility for assistance in cell
sorting and image quantification. K.M. is supported by the European Community’s Seventh
Framework Programme PRIME-XS (262067) and MeioSys (222883-2) and from the Austrian
Science Fund SFB F3402, P24685-B24 and TRP 308-N15. K.K. was supported by a grant of
the Medical University of Vienna, and in part by a grant from the FWF (FWF-P-25333-B08).
C.K. is supported by the ERC, an EU ERARE program (NEUTRO-NET), the DFG GottfriedWilhelm-Leibniz program, DFG-SFB914 (Migration of Immune Cells) and the DZIF (German
Center for Infection Research). J.M.P. is supported by grants from IMBA, the Austrian National
Foundation, the Austrian Academy of Sciences, NEUTRO-NET, and an EU ERC Advanced Grant.
Contact / E-Mail:
[email protected]
- 36 -
Daniela GALLERANO(1), Portia NDLOVU(2), Ian MAKUPE(2), Margarete FOCKE-TEJKL(1),
Kerstin FAULAND(3), Eva WOLLMANN(1), Elisabeth PUCHHAMMER-STÖCKL(4), Walter
KELLER(3), Elopy N. SIBANDA(5) and Rudolf VALENTA(1)
We studied epitope specificities of antibody responses in HIV-infected patients from SubSaharan Africa, where clade C is prevalent, and in patients from Europe, where infections are
predominantly caused by clade B.
A comprehensive set of HIV-1 clade C recombinant proteins and peptides derived from
envelope proteins gp120 and gp41 was prepared, purified and used to measure IgG, IgGsubclass, IgA and IgM responses in the two populations and in African follow-up serum
samples.
Interestingly, African and European patients showed almost identical antibody reactivity
profiles in terms of epitope specificity and involvement of IgG, IgG-subclass, IgA and IgM
responses. Among gp120-derived peptides, the major epitopes were a peptide overlapping
the V3 region and a C-terminal peptide, which were recognized by IgG1>IgG2=IgG4>IgG3,
IgA>IgM and by the four IgG-subclasses, respectively. By contrast, gp41-derived-peptides
were mainly recognized by IgG1 but not by the other IgG-subclasses, IgA or IgM. Among
non-surface proteins, protease, reverse transcriptase+RNAseH, integrase, capsid and matrix
proteins were the most frequently and strongly recognized antigens which showed broad IgGsubclass and IgA reactivity. Immune recognition of gp120 peptides and non-surface proteins
involved all four IgG-subclasses and was indicative of a mixed Th1/Th2 immune response.
Specificities and magnitudes of antibody responses in African patients were stable during
disease and antiretroviral treatment, and persisted despite severe T cell loss.
The HIV-1 clade C proteome-based test therefore allowed diagnosis and monitoring of antibody
responses during the course of HIV-infections and assessment of specificity, isotype and
subclasses.
Oral Presentation
(1) Division of Immunopathology, Department of Pathophysiology and Allergy Research,
Medical University of Vienna, Austria
(2) Gamma City Laboratory, Harare, Zimbabwe
(3) Institute of Molecular Biosciences - Structural Biology, Karl Franzens University, Graz,
Austria
(4) Department of Virology, Medical University of Vienna, Austria
(5) Asthma, Allergy and Immune Dysfunction Clinic, Parirenyatwa University Teaching Hospital,
Harare, Zimbabwe
Abstract 8
Mapping of IgG, IgG-subclass, IgA and IgM reactivity
profiles in African and European HIV-infected
individuals with an HIV-1 clade C proteome-based
array
Acknowledgements
This study was supported by a research grant from Biomay AG, Vienna, Austria.
Contact / E-Mail:
[email protected]
- 37 -
Oral Presentation
Abstract 9
Identification of a lipid-modifying enzyme as novel
regulator of innate immune responses
Leonhard X. HEINZ(1), Christoph L. BAUMANN(1), Marielle KÖBERLIN(1), Berend SNIJDER(1),
Manuela BRUCKNER(1), Riem GAWISH(1), Omar SHARIF(1), Kumaran KANDASAMY(1),
Jacques COLINGES(1), Keiryn L. BENNETT(1), Astrid FAUSTER(1), Guanghou SHUI(2), Sylvia
KNAPP(1), Markus R. WENK(2) and Giulio SUPERTI-FURGA(1)
(1) CeMM, Research Center for Molecular Medicine of the Austrian Academy of Sciences,
Vienna, Austria
(2) Department of Biochemistry, Yong Loo Lin School of Medicine, National University of
Singapore, Republic of Singapore
Lipid metabolism and receptor-mediated signaling are highly intertwined processes that
cooperate to fulfill cellular functions and conspire to safeguard cellular homeostasis. Therefore,
modulation of the cellular lipid landscape offers an excellent opportunity to globally adapt to
environmental changes. Activation of Toll-like receptors (TLRs) leads to a complex cellular
response, orchestrating a diverse range of inflammatory processes that need to be tightly
controlled. Here we report the identification of a lipid-modifying enzyme as novel GPIanchored negative regulator of TLR signaling. Loss-of-function in macrophages led to a
higher responsiveness upon TLR stimulation and knock-out mice manifested enhanced proinflammatory responses in TLR-dependent models, confirming our data in vivo. Revealing a
role in lipid metabolism, knockdown of the enzyme profoundly changed both the global lipid
composition and membrane fluidity. Lipidomics-based functional mapping of changes in lipid
species abundance were predictive of its anti-inflammatory properties, mechanistically linking
membrane lipid composition and innate immune signaling. Taken together, our results identify
a membrane-modulating enzyme as novel regulator of innate immune signaling.
Acknowledgements
This work was funded by the Austrian Academy of Sciences and the European Research
Council.
Contact / E-Mail:
[email protected]
- 38 -
A. WAGNER(1), E. GARNER-SPITZER(1), J. JASINSKA(1), M. PAULKE-KORINEK(1), M.
HOFER(1), K. STIASNY(2), F. X. HEINZ(2), H. KOLLARITSCH(1), U. WIEDERMANN(1, 3)
(1) Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna,
Kinderspitalgasse 15, 1090 Vienna, Austria
(2) Medical University of Vienna, Department of Virology, Vienna, Austria
(3) Department of Rheumatology & Inflammation Research, Institute of Medicine, University of
Göteborg, Sweden
Oral Presentation
Immunosenescence is associated with reduced B and T cell responses. It has been shown that
booster vaccination is less effective in the elderly. However data on the efficacy of primary
immunisation in the elderly is sparse. In a monocentric, open label, phase IV study we
investigated humoral and cellular immune responses to primary Japanese Encephalitis (JE)
vaccination in young (18-40 y) and elderly subjects (>60 y).
All subjects (30/ group) received a primary course of an inactivated JE- vaccine. Neutralising
antibody titers (NT) were determined in serum samples taken before vaccination, 1 and 5
weeks after the 2nd dose. PBMC´s were isolated prior to the 1st and 1 week after the 2nd dose
for analysis of different T- and B-cell subsets and antigen restimulation.
JE-NT´s were significantly lower in elderly compared to young participants. Furthermore 47%
of the elderly were no/low-responders to JE-vaccination. Reduced humoral immune responses
were associated with reduced cytokine production (e.g. IFN-g) in vitro and a significant
increase of Treg cells in the elderly. Additionally, higher frequencies of late-differentiated
effector and effector memory cells were detected in elderly. The majority of elderly subjects
were seropositive for CMV, which correlated with reduced antibody
Abstract 10
Age-related differences of humoral and cellular
immune responses to primary Japanese Encephalitis
vaccination
Contact / E-Mail:
[email protected]
- 39 -
Oral Presentation
Abstract 11
The impact of an acute allergic inflammation on
neurogenesis and microglia in the hippocampal
dentate gyrus
Barbara KLEIN(1,2), Richard WEISS(3), Sebastien COUILLARD-DESPRES(2,4), Josef
THALHAMER(3), Ludwig AIGNER(1,2)
(1) Institute of Molecular Regenerative Medicine, Paracelsus Medical University Salzburg
(2) Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus
Medical University Salzburg
(3) Division of Allergy and Immunology, Department of Molecular Biology, University of
Salzburg
(4) Institute of Experimental Neuroregeneration, Paracelsus Medical University Salzburg
Our aim was to investigate the effect of an acute allergic inflammation on the hippocampal
neurogenic niche in C57BL/6 mice. For sensitization, we used the timothy grass pollen
allergen Phl p 5 and aluminum hydroxide followed by intranasal challenges with Phl p 5 four
days before the end of the experiment. Blood levels of Phl p 5-specific IgE, IgG1 and IgG2a
confirmed sensitization. Immunohistochemical analyses of proliferating cell nuclear antigen
(PCNA) or bromodeoxyuridine (BrdU), injected four weeks before the end of the experiment,
showed that the allergy group had higher cell proliferation in the hippocampal neurogenic niche
compared to controls. Co-labelling of BrdU with NeuN (a marker for mature neurons) or glial
fibrillary acidic protein (GFAP), showed that numbers of newly generated neurons (NeuN+) and
GFAP+ astrocytes increased significantly in comparison to controls. In the same region, also
more immature neurons expressing doublecortin (DCX) were found. Interestingly, fewer cells
were positive for ionized calcium binding adaptor molecule-1 (Iba-1), a marker for microglia,
and their soma was smaller. These results indicate that an acute allergic inflammation not
only leads to altered microglial activity in the hippocampal dentate gyrus, but also affects
neurogenesis.
Acknowledgements
This project is supported by the Research Fund of the Paracelsus Medical University Salzburg
(PMU-FFF) as a RISE Project under grant agreement R-13/02/046-KLE.
Contact / E-Mail:
[email protected]
- 40 -
MACHADO Yoan(1), MAYR Melissa(1), THALHAMER Theresa(1), HÖPFLINGER Veronika(1),
SCHEIBLHOFER Sandra(1), THALHAMER Josef(1), WEISS Richard(1)
(1) University of Salzburg, Department of Molecular Biology, Division of allergy and
Immunology, Hellbrunnerstrasse 34, Salzburg
Oral Presentation
Due to its abundance of APCs, the skin represents an attractive target tissue for specific
immunotherapy. Recently, we demonstrate the feasibility of efficiently targeting APCs through
C-type lectin receptors using hypoallergenic neoglycoconjugates of papain with mannan.
Here, a panel of polysaccharides, mannan, laminarin, glucomannan, inulin and dextran were
efficiently coupled to Bet v 1.0101. Mice were immunized with these neoglycoconjugates
via laser porated skin and the immunogenicity and cytokine profile elicited were measured.
Allergenicity of Bet v 1.0101 glycoconjugates could be modulated by varying the sugarto-protein ratio achieving an up to 1000-fold reduction in IgE cross linking capacity. In
vitro uptake experiments using BMDCs revealed an increased uptake for Bet-Mannan
neoglycoconjugates compared to Bet v 1.0101. Mice immunized with these neoglycocojugates
showed high IgG1 and IgG2a antibodies. Bet-Mannan neoglycoconjugates shifted the immune
response to a Th1/Th17 pattern evidenced by large amount of IL-17 and IFN-γ secreted by
Bet v 1.0101 re-stimulated splenocytes isolated from immunized mice. These data suggest
coupling carbohydrates to Bet v 1.0101 as an attractive approach for pollen allergen specific
cutaneous immunotherapy.
Abstract 12
Carbohydrate coupling as a tool for modulation of
the allergenicity and immunological properties of the
major birch pollen allergen Bet v 1.0101
Acknowledgements
This work was supported by the Austrian Science Fund (FWF Project # W1213).
Contact / E-Mail:
[email protected]
- 41 -
Oral Presentation
Abstract 13
Phosphorylation of CREB is upregulated in
keratinocytes after treatment with the major birch
pollen allergen, Bet v 1, and birch pollen lipids
Barbara GEPP(1), Nina LENGGER(1), Christian RADAUER(1), Florian GRUBER(2), Michael
MILDNER(2), Heimo BREITENEDER(1)
(1) Department of Pathophysiology and Allergy Research, Center for Pathophysiology,
Infectiology and Immunology, Medical University of Vienna
(2) Department of Dermatology, Medical University of Vienna
Lipids accompanying or binding to allergens can be immunomodulating. Therefore, we
analyzed the ability of the major birch pollen allergen, Bet v 1, to bind lipids from peanut,
birch or grass pollen and tested the phosphorylation of the transcription factor CREB in primary
keratinocytes after stimulation with Bet v 1 alone or Bet v 1 in combination with lipids.
Total lipids from peanut, birch and grass pollen were extracted using chloroform/
methanol. The binding of lipids to the hydrophobic cavity of Bet v 1 was verified by adding
1-anilinonaphthalene-8-sulfonic acid (ANS) and measuring the decrease of fluorescence at 484
nm. Phosphorylated CREB (p-CREB) levels were analyzed by Western Blot.
After incubation of Bet v 1 with lipid extracts from both pollen species but not from peanut,
a concentration dependent reduction of ANS binding was observed. Furthermore, Bet v 1 in
combination with birch pollen lipids showed higher levels of p-CREB in keratinocytes compared
with birch pollen lipids alone.
The increased phosphorylation of CREB after treatment with Bet v 1 in combination with birch
pollen lipids indicates that Bet v 1 may act as a transport vehicle able to release lipids to cell
membranes and therefore providing a potential danger signal during the sensitization phase.
Acknowledgements
Supported by grant SFB-F4608 (HB) from the Austrian Science Fund.
Contact / E-Mail:
[email protected]
- 42 -
RAFFAELA CAMPANA(1), Katharina MORITZ(2), Angela NEUBAUER(3), Hans HUBER(3), Rainer
HENNING(3), Katharina BLATT(4), Gregor HOERMANN(5), Tess M. BRODIE(6), Alexandra
KAIDER(7), Peter VALENT(4), Federica SALLUSTO(6), Stefan WÖHRL(2), Rudolf VALENTA(1,*)
Oral Presentation
(1) Division of Immunopathology, Department of Pathophysiology, Center of Physiology and
Pathophysiology, Vienna General Hospital (AKH), Medical University of Vienna, Austria; (2)
Division of Immunology, Department of Dermatology, Allergy and Infectious Diseases, Vienna
General Hospital (AKH), Medical University of Vienna, Austria; (3) Biomay AG, Vienna, Austria;
(4) Division of Hematology and Hemostaseology, Department of Internal Medicine I, Vienna
General Hospital (AKH), Medical University of Vienna, Austria; (5) Department of Laboratory
Medicine, Vienna General Hospital (AKH), Medical University of Vienna, Austria; (6) Cellular
Immunology Laboratory, Institute for Research in Biomedicine, Bellinzona, Switzerland;
(7) Center for Medical Statistics, Informatics and Intelligent Systems, Section for Clinical
Biometrics, Medical University of Vienna, Austria.
Abstract 14
Epicutaneous application of recombinant Bet v 1 and
Bet v 1 derivatives induces allergen-specific IgG and
T cell responses
Allergen-specific immunotherapy (SIT) is the only allergen-specific and disease-modifying
treatment for allergy but can induce side effects and suffers from inconvenient administration
protocols. We have conducted a clinical trial using rBet v 1 and two hypoallergenic rBet v 1
fragments for epicutaneous administration (i.e., atopy patch testing) in 30 adult subjects (15
birch pollen allergic patients suffering from AD, 5 birch pollen-related RC patients, 5 allergic
patients without birch pollen allergy and 5 non-allergic individuals). Blood samples were
collected before and 6-8 weeks after application and used to compare allergen-specific IgE
and IgG antibody levels, T cell and cytokine responses. Epicutaneous administration of rBet v
1 and rBet v 1 derivatives leads to a significant boosting of allergen-specific T cell proliferation
and IgG production mainly in APT-positive birch pollen allergic patients, but not IgE production.
In these patients significant increases in skin-homing CLA+ and CCR4+ T cells were observed
after allergen administration. No systemic side effects were observed. Our results demonstrate
that epicutaneous application of recombinant allergens boosts allergen-specific T cell and IgG
antibody responses and thus may be considered as a possible route for SIT.
Acknowledgements
Supported by the Austrian Science Fund (FWF), Vienna, Austria.
Contact / E-Mail:
[email protected]
- 43 -
Oral Presentation
Abstract 15
Azithromycin inhibits IL-1 beta secretion of innate
immune cells by specificly inhibiting the NLRP3
inflammasome
Guido A. GUALDONI(1), Tilman R. LINGSCHEID(2), Peter STEINBERGER(1), Gerhard J.
ZLABINGER (1)
(1) Institute for Immunology, Center for Pathophysiology, Infectiology and Immunology,
Medical University of Vienna
(2) Department of Internal Medicine/Infectious Diseases and Pulmonary Medicine, Charité
-- Universitätsmedizin Berlin, Germany
Macrolides are a class of antibiotics widely used in the treatment of infectious diseases,
azithromycin being one of the most prominent representatives. In addition to its antiinfective qualities, immune-modulating properties have been attributed to these substances,
an effect which is being increasingly exploited in clinical medicine. However, the molecular
impact on immune cell function remains poorly characterized. Investigating the cytokinemodulatory properties of azithromycin in human monocytes, we found a specific inhibition of
IL-1 beta secretion upon LPS stimulation, whereas no significant effect was seen upon flagellin
stimulation, thus indicating a specific effect on the NLRP3 inflammasome. Coherently, we found
inhibition of caspase-1 cleavage whereas NF-kappaB signaling was unaffected. In contrast,
other macrolides tested, did not alter cytokine production. Furthermore, our findings were
confirmed in a murine endotoxin sepsis model, in which azithromycin treatment resulted in
a specific IL-1 beta down-modulation and enhanced survival. Overall, we provide evidence of
a novel facet of azithromycin’s immune-modulation which might help to better understand
clinical observations and lead to novel applications of this well established drug.
Acknowledgements
The authors thank Petra Waidhofer-Söllner for excellent technical assistance.
Contact / E-Mail:
[email protected]
- 44 -
Anastasia MESHCHERYAKOVA(1), Erika BAJNA(1), Susanne WÖHRER(1)
Elfi SCHARF(1), Martin SVOBODA(1), Erika JENSEN-JAROLIM(1,2), Georg HEINZE(3), Peter
BIRNER(4), Diana MECHTCHERIAKOVA(1)
Ovarian cancer comprises a highly heterogeneous multifactorial disorder. Increasing attention
is given to the role of local inflammation and tumor infiltrating immune cells in disease
etiology. In the current study we asked whether patient-specific immunological imprint might
be used as prognostic marker for estimation of disease development and clinical outcome.
To get comprehensive overview, we examined large cohort of patients with primary ovarian
cancer (n=67). Microscopy-based platform was used for automatic scanning and follow up
quantitative analysis. Focus of the study was given to the CD45-positive leukocyte population,
CD20-positive B lymphocytes and CD68-positive monocytes/macrophages. Unique advantage
of this system provides opportunity to align the quantities of individual immune cell subpopulations with their spatial distribution accounting for tumor anatomy. Staining-derived
datasets are used for alignment with clinical parameters and for building up of prognostic
models, thus reflecting the individual impact of B-cell and macrophage lineages and their
potential mutual interconnection. Such strategy represents an innovative approach toward
patient’ stratification for prognostic monitoring and might open new directions for patientorientated therapeutic interventions.
Key words: Tumor immunology, patient-orientated immunological imprint
Oral Presentation
(1) Department of Pathophysiology and Allergy Research, Center of Pathophysiology,
Infectiology & Immunology, Medical University of Vienna, Austria
(2) Messerli Research Institute of the Medical University of Vienna, Veterinary University of
Vienna and University of Vienna, Austria
(3) Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of
Vienna, Austria
(4) Clinical Institute of Pathology, Medical University of Vienna, Austria
Abstract 16
Patient-specific immunological imprint within
complex ovarian cancer tissues
Acknowledgements
The work was supported by The Austrian Science Fund FWF P22441-B13 and P23228-B19
Contact / E-Mail:
[email protected]
- 45 -
Oral Presentation
Abstract 17
Innate responses and antigen-presenting capacity of
oral epithelial cells
Claudia KITZMÜLLER(1), Martina SCHUSCHNIG(1), and Barbara BOHLE(1)
(1) Christian Doppler Laboratory for Immunomodulation, Department of Pathophysiology and
Allergy Research, Medical University Vienna
Background: Epithelial cells of the oral cavity have important barrier functions and might be
involved in the development of oral tolerance. Little is known about their possible role in the
modulation of immune responses.
Aim: To analyse whether oral epithelial cells react to pathogen-associated molecular patterns
(PAMPs) and up-regulate components of the antigen-processing and -presentation machinery
under inflammatory or infectious conditions.
Methods: We analysed the expression of Toll-like receptors (TLR), NOD-like receptors (NLR)
and C-type lectin receptors (CLR) by the buccal epithelial cell line HO-1-N-1, the sublingual
epithelial cell line HO-1-u-1 as well as by primary human oral keratinocytes (HOK) using PCR
and studied the functional response of receptor stimulation by IL-8 ELISA. We used Western
Blot and flow cytometric analysis to check whether the cell lines up-regulate Cathepsin S and
MHC class I and II molecules in response to direct stimulation with IFN-gamma and indirect
stimulation by PAMPs.
Results: HO-1-N-1 expressed mRNA of TLR 1, 2, 4, 6 and NOD1 and increased IL-8 production
after stimulation of TLR 2, 3, 4 and NOD1. HO-1-u-1 expressed mRNA of TLR 1, 3, 4, 5, 6, and
NOD1 and secreted elevated levels of IL-8 after stimulation of TLR 3 and 5. HOK expressed
mRNA of all the TLR and NLR analysed and reacted strongly to TLR 3 stimulation and less
to a TLR 2 ligand. Direct stimulation with IFN-g led to an up-regulation of Cathepsin S and
an increased expression of MHC class I and II molecules on the surface HO-1-N-1 and HOK.
In ongoing experiments we found so far that HOK can increase the levels of MHC class I
molecules also after stimulation of TLR 3.
Conclusion: Oral epithelial cells can be stimulated by TLR ligands. Depending on whether their
origin is from buccal and sublingual regions they show differences to which stimuli they react
to. Under inflammatory and infectious conditions oral epithelia could have antigen-presenting
potential.
Acknowledgements
Supported by the Christian Doppler Research Association, Biomay
AG, Austria, and the Austrian Science Fund, projects SFB F4610, W1212 and W1213
Contact / E-Mail:
[email protected]
- 46 -
Douglas F. PINHEIRO(1), Megan M. MAURANO(1), Abul K. ABBAS(3), Iris K. GRATZ(1,2,4)
(1) Department of Molecular Biology, University of Salzburg, Salzburg, Austria
(2) Department of Dermatology, University of California San Francisco, San Francisco,
CA 94143, USA
(3) Department of Pathology, University of California San Francisco, San Francisco,
CA 94143, USA
(4) Division of Molecular Dermatology and EB House Austria, Department of Dermatology,
Paracelsus Medical University, Salzburg, Austria
Oral Presentation
Immune homeostasis in tissues is achieved by maintaining a delicate balance between
pathogenic effector T cells (Teff) and protective regulatory T cells (Treg) specific for tissueantigens (Ags). The factors responsible for maintaining this balance are largely unknown.
Previous findings from our group suggest that tissues acquire the ability to attenuate
autoimmune reactions upon repeated exposure to Ags. However, the mechanism by which this
occurs is unknown.
To study immune regulatory mechanisms in a T cell mediated autoimmune disease, we
established two mouse models that feature tetracycline-inducible expression of chicken
ovalbumin (Ova) in the epidermis. Expression of Ag in the skin elicits a T cell dependent
inflammatory dermatitis. Using this model, we found that Ag persistence is a major
determinant of the relative frequencies of Teff and Treg cells. Persistent Ag, a mimic of self Ag,
lead to functional inactivation and loss of the Teff cells with preservation of Treg cells in the
target tissue, both of which was associated with reduced ERK phosphorylation. Additionally, we
found that the Ag dose determines early T cell differentiation decisions in vivo. These findings
provide a framework for understanding how Treg and Teff cells respond to self-Ag in peripheral
tissues.
Abstract 18
Controlling the balance between effector and
regulatory T cells in peripheral tissues
Acknowledgements
This work has been supported by grants to Iris K. Gratz from the NIH (AR064554), the
Austrian Science Fund (FWF) (J2997-B13) and by the Dystrophic Epidermolysis Bullosa
Research Association (DEBRA) International and DEBRA Austria.
Contact / E-Mail:
[email protected]
- 47 -
Oral Presentation
Abstract 19
Dual Role of NSAIDs: overcoming melanoma
resistance and enhancing cytotoxic potential of
innate immune cells.
Mariana VÁZQUEZ-STRAUSS, Georg STINGL
DIAID, Medical University of Vienna, Vienna, Austria.
As opposed to other solid carcinomas, melanoma is sometimes amenable to immunotherapy.
In fact, we found that some, but not other, melanoma cell lines undergo lysis when treated
with the soluble form of the lytic molecule TNF-related apoptosis-inducing ligand (TRAIL) and
that the non-steroidal anti-inflammatory drug (NSAID) diclofenac can sensitize otherwise
resistant cell lines to TRAIL-induced apoptosis. When we addressed the mechanisms underlying
the latter phenomenon, we found that diclofenac induces upregulation of (i) the pro-apoptotic
receptor TRAIL-R2 and (ii) pro-apoptotic molecules such as caspases 5 and 10, NOXA, CYCS,
CHOP and XBP1 in melanoma cells. Surprisingly enough, Diclofenac proved to be equally
effective as imiquimod in upregulating TRAIL expression on diverse leukocyte subpopulations
(e.g. monocytes, mDCs, pDCs). In light of these results it appears that the anti-tumoral effects
of diclofenac and probably also other NSAIDs are due to, at least, a bimodal action, i.e. by
increasing the susceptibility towards lysis of the tumor cells as well as the tumoricidal potential
of leucocytic effector cells.
Acknowledgements
FWF PhD Programm “Inflamation and Immunity”.
Contact / E-Mail:
[email protected]
- 48 -
Elisabeth GLITZNER(1), Ana KOROSEC(1), Patrick M. BRUNNER(2), Barbara DROBITS(1),
Nicole AMBERG(1), Helia B. SCHONTHALER(3), Tamara KOPP(2), Erwin F. WAGNER(3), Georg
STINGL(2), Martin HOLCMANN(1), Maria SIBILIA(1)
(1) Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center,
Medical University of Vienna, Vienna, Austria
(2) Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases,
(3) BBVA Foundation–CNIO Cancer Cell Biology Programme, Spanish National Cancer Research
Centre (CNIO), Madrid, Spain
Oral Presentation
Several subtypes of dendritic cells (DCs) are found in skin lesions of psoriasis patients, but
their involvement in disease pathogenesis is poorly understood. Here, we investigated a
contribution of Langerhans cells (LCs) and plasmacytoid DCs (pDCs) in psoriasis. In both
human psoriatic lesions and a psoriasis mouse model (DKO* mice), LC numbers are severely
reduced, whereas pDC numbers are increased. Depletion of pDCs in DKO* mice prior to
psoriasis induction resulted in a milder phenotype, whereas pDC depletion during established
disease had no effect. In contrast, depletion of Langerin+ APCs before disease onset did not
affect psoriasis development, whereas depletion from psoriatic DKO* mice aggravated disease
symptoms. Using bone marrow (BM) chimeric mice, we found that disease aggravation was
due to absence of LCs, but not other Langerin+ APCs, and that LC replenishment in psoriasis
occurred from BM-derived precursors. LCs produced high levels of IL-10 in psoriatic mice, and
LC depletion resulted in increased epidermal IL-23. In the absence of pDCs, IL-23 production
was reduced, and blocking of IL-23R signaling greatly ameliorated disease symptoms. These
results demonstrate that LCs exert an anti-inflammatory function during active psoriatic
disease, while pDCs have an instigatory effect during disease initiation via IL-23 production.
Abstract 20
Specific roles for dendritic cell subsets during
initiation and progression of psoriasis
Contact / E-Mail:
[email protected]
- 49 -
Oral Presentation
Abstract 21
The role of Langerhans cells and natural killer cells
in cancer immune surveillance
Daniela ORTNER(1), Christoph TRIPP(1), Nicole AMBERG(2), Maria SIBILIA(2), Björn E.
CLAUSEN(3) and Patrizia STOITZNER(1)
(1)Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck,
Austria
(2)Department of Medicine I, Institute for Cancer Research, Medical University of Vienna,
Vienna, Austria
(3) Institute for Molecular Medicine, University Medical Center of the Johannes GutenbergUniversity Mainz, Mainz, Germany
Non-melanoma skin cancers like basal cell carcinoma (BCC) are the most common skin
tumors. These epithelial tumors develop in the basal layers of the epidermis due to UV
exposure or chemical carcinogenesis. The aberrant activation of the hedgehog signaling
pathway has been detected as one of the major genetic causes for BCC. A transgenic mouse
model harboring an inducible activating allele of the hedgehog protein Smoothened (R26SmoM2) develops skin alterations similar to BCC. We have attained first results using this
mouse model showing that natural killer cells (NK) and Langerhans cells (LC) disappear from
skin during tumorigenesis. Mice developing BCC were crossed with a mouse model that allows
depletion of langerin-positive skin DC, which led to a higher tumor burden. These observations
indicate that NK cells and LC are important for immunosurveillance early in tumorigenesis.
Investigating the cytokine milieu in skin upon tumor progression showed an enhanced
inflammatory and tumor-permissive environment with significantly increased IL-1β, TNF-α and
TGF-β mRNA levels. Furthermore, tumor-bearing skin contained a huge population of CD11b+
Gr1+ cells, most likely myeloid derived suppressor cells. The interactions of these various
immune cell types in the tumor situation need to be further investigated to understand how
innate immune responses are altered during carcinogenesis. The elimination of NK cells and LC
could be a potent tumor escape mechanism in BCC.
Contact / E-Mail:
[email protected]
- 50 -
Nazanin SAMADI, Claudia KITZMÜLLER , Barbara BOHLE, Rene GEYEREGGER, Beatrice JAHNSCHMID
Department of Pathophysiology and Allergy Research,
Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna
Oral Presentation
Allergy is the abnormal immune response against harmless antigens. Like any immune
response, allergic reactions are mediated by both innate and adaptive immunity. T cells are
part of adaptive immunity and play a main role in the development of type I allergy. The
function of CD4+T cells in the pathogenesis and maintenance of allergic disorders have been
broadly investigated while the role of CD8+T cells is poorly understood. Previous studies
have demonstrated a controversial function of CD8+T cells in allergic disorders in human and
murine models. The aim of this project is to identify and characterize allergen-specific CD8+ T
cells in patients with different manifestations (rhinoconjunctivitis, atopic dermatitis and atopic
bronchial asthma) of type I allergy. Different seasonal and perennial allergens will be studied.
Allergen specific T cells from PBMCs will be expanded in vitro and these T cell lines and cloned
T cells will be characterized for their phenotype and function. By now, we have optimized
the expansion of allergen-activated CD8. Peripheral blood from patients were stained by
proliferation dyes and stimulated with allergen. Proliferating cells were expanded by addition
of growths factor/s in short time cultures and characterized. We could find significant CD8+T
cell proliferation in all allergic diseases, but larger numbers of allergen-reactive CD8+T cells
were found in T cell lines induced by cat hair and house dust mite extracts compared to pollen
extracts from birch and grass. Further experiments are needed to identify the functionality of
these allergen-reactive CD8+ T cells.
Abstract 22
Characterization of the CD8+ T cell response to
allergens
Acknowledgements
Supported by the Austrian Science Funds, project W1248.
Contact / E-Mail:
[email protected]
- 51 -
Oral Presentation
Abstract 23
Does signal one strength influence the phenotype
and function of human allergen-specific T
lymphocytes?
Martín R. CANDIA(1), Peter TAUBER(1), Alina NEUNKIRCHNER(1,2), Doris TRAPIN(1), Sandra
ROSSKOPF(1), Peter STEINBERGER(1) and Winfried F. PICKL(1,2).
(1) Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology,
(2) Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna,
Austria.
TCR signal strength is a major relaying mechanism to control T cell differentiation and function.
Since allergic sensitization but also late phase allergic reactions have been linked to altered
CD4+ T cell function, we sought to investigate the contribution of TCR signal strength to the
differentiation of allergen-specific CD4+ Th cells. We here used a recently developed Art v 1
TCR/HLA-DRB1*01:01 double transgenic system to define possible altered peptide ligands
(APL) of the major mugwort pollen allergen, Art v 1(24-35). Furthermore, variation of the
amount of antigenic peptides as well as targeted pharmacological inhibition of T cell signaling
pathways was used to alter signal strength. For the quick and facile determination of the
binding characteristics of APL a robust, flow cytometry-based assay for peptide binding to
cell surface expressed HLA molecules was established. So far, two APL with differential T cell
activating capabilities as determined by proliferation and cytokine secretion assays have been
characterized. Moreover, some targeted drugs could be identified, which resulted in differential
cytokine production in allergen-specific T cells. In summary, altering TCR signal strength might
represent a useful way how to shape allergen-specific T cellular immune responses.
Acknowledgements
Supported by the Austrian Science Fund (FWF) project DK-W1248-B13 (as part of the PhD
program Molecular, Cellular and Clinical Allergology, MCCA of the Medical University of Vienna),
SFB F46909-B19 and Biomay AG.
Contact / E-Mail:
[email protected]
- 52 -
Susanne C. DIESNER(1,2), Cornelia SCHULTZ(1), Chloé ACKAERT(3), Gertie J.
OOSTINGH(4), Anna ONDRACEK(1), Caroline STREMNITZER(1), Denise HEIDEN(1), Josef
SINGER(1), Franziska ROTH-WALTER(1,5), Judit FAZEKAS(1), Thomas EIWEGGER(2), Zsolt
SZÉPFALUSI(2), Erika JENSEN-JAROLIM(1,5), Ernst-Hanno STUTZ(3), Albert DUSCHL(3) and
Eva UNTERSMAYR(1)
Oral Presentation
(1) Department of Pathophysiology and Allergy Research, Divison of Comparative Immunology
and Oncology, Center of Pathophysiology, Infectiology and Immunology, Medical University of
Vienna, Vienna, Austria.
(2) Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna,
Austria.
(3) Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
(4) Biomedical Sciences, Salzburg University of Applied Sciences, Puch/Salzburg, Austria.
Vienna, Medical University Vienna and University Vienna, Vienna, Austria.
Abstract 24
Nitrated Beta-Lactoglobulin enhances the
anaphylactic response in a murine food allergy
model
We reported that nitrated food proteins have a reduced de novo sensitization capacity.
Conversely, in vitro experiments showed an enhanced effector cell triggering capacity. Thus,
we aimed to investigate the influence of nitration on the effector phase of food allergy.
BALB/c mice were repeatedly immunized intraperitoneally with the milk allergen betalactoglobulin (b-LG) or the egg allergen ovomucoid (OVO) followed by two intragastric
feedings. Thereafter, mice were systemically challenged with untreated, sham-nitrated or
nitrated b-LG or OVO to evaluate their allergic response. The anaphylaxis marker mMCP1 was
significantly elevated only in b-LG allergic animals challenged with nitrated b-LG compared to
those challenged with untreated or sham-nitrated b-LG. This was confirmed by a significant
drop of body temperature. Interestingly, this effect was not observed for OVO. Circular
dichroism and SDS-PAGE analysis revealed an impact of nitration on the secondary structure
exclusively for b-LG together with enhanced protein dimerization.
Our data indicate that nitration differently affects the food allergens b-LG and OVO. In case
of b-LG, nitration influenced the secondary structure and favoured dimerization causing an
enhanced anaphylactic capacity in b-LG allergic animals.
Acknowledgements
Supported by the Austrian science fund project P21577-B11 and by the Wirtschaftkammerpreis
2014.
Contact / E-Mail:
[email protected]
- 53 -
Oral Presentation
Abstract 25
The trimeric complex of recombinant CD23 together
with allergen and allergen-specific IgE
Regina M. Selb(1), Julia Eckl-Dorna(1), Christian Lupinek(2), Birgit Linhart(2), Andrea
Teufelberger(3), Walter Keller(3), Kenneth H. Roux(4), Rudolf Valenta(2) and Verena
Niederberger(1)
(1)Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria
(2)Divison of Immunopathology, Department of Pathophysiology and Allergy Research, Center
for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria
(3)Institute of Molecular Biosciences, Karl Franzens University, Graz, Austria
(4)Florida State University, Tallahassee, Florida, USA
CD23, the low affinity receptor for IgE, plays an important role in allergy. One major function
is the IgE-facilitated allergen presentation to T cells and subsequent activation of allergenspecific T cells.
Four CD23 protein versions were recombinantly expressed in SF9 insect cells. The
characterisation via circular dichroism (CD) spectra and gel filtration showed folded,
monomeric proteins. Binding of both monomeric human monoclonal and polyclonal serum
IgE as well as IgE in complex with birch pollen allergen Bet v 1 to CD23 was demonstrated by
ELISA and by surface plasmon resonance.
We performed negative stain electron microscopy of the three molecules alone (i.e., CD23,
monoclonal human IgE, Bet v 1) and after complex formation. After addition of Bet v 1 allergen
(17 kDa) to monoclonal IgE (190 kDa) we observed an extension of one or both Fab arms
of the antibody. Further addition of recombinant CD23 molecules (35 kDa) to the complex
resulted in thickening of the antibody’s Fc structure in our pictures.
In summary, we report the in vitro formation of a tri-molecular complex consisting of
recombinant CD23, monoclonal allergen-specific IgE and Bet v 1 and take a first step towards
the visualization of this complex by negative stain electron microscopy.
Acknowledgements
Supported by grants 4605, 4613 and in part by 4604 and P23350-B11 of the Austrian Science
Fund (FWF).
Contact / E-Mail:
[email protected]
- 54 -
Marion STEGER(1), Emina JUKIC(1), Wilfried POSCH(1), Cornelia LASS-FLÖRL(1), Hubertus
HAAS(2), Doris WILFLINGSEDER(1)
(1) Division of Hygiene and Medical Microbiology, Innsbruck Medical University
(2) Division of Molecular Biology, Innsbruck Medical University, Innsbruck, Austria
Oral Presentation
In this study, interactions of dendritic cells (DCs) with differentially opsonized and nonopsonized Aspergillus fumigatus strains were investigated. Two different mutants were used,
one lacking the pigment melanin (pksP mutant) and one the hydrophobin layer (rodA mutant).
Opsonization pattern of the different strains, binding and internalization by DCs as well as
cytokine secretion were studied. We demonstrated that melanin has the highest impact on
the fungal virulence compared to the wildtype Aspergillus strain. Surprisingly, the rodlet layer
showed a minor impact on complement (C) activation. C coating of conidia enhanced these
processes compared to their non-opsonized counterparts independent on the fungal strain
used. These data revealed, that melanin is one of the key effectors of masking C deposition
and binding of conidia by DCs. Opsonization of swollen conidia favored the uptake and
internalization and production of pro-inflammatory cytokines, resulting in a favorable TH1
immune response. These in vitro studies propose DCs or neutrophils in combination with
complement opsonins as possible vaccines against invasive aspergillosis.
Abstract 26
Complement opsonization of A.fumigatus modifies
dendritic cell maturation and up-take
Contact / E-Mail:
[email protected]
- 55 -
Oral Presentation
Abstract 27
Failure of specific immunotherapy (SIT) with house
dust mite (HDM) allergen extracts due to lack of
HDM allergens capable of inducing specific IgG
responses in the therapeutic extracts
Kuan-Wei CHEN (1), René ZIEGLMAYER (2), Petra ZIEGLMAYER (2), Patrick LEMELL (2),
Friedrich HORAK (2), Rudolf VALENTA (1), Susanne VRTALA (1)
(1) Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center
for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria
(2) Vienna Challenge Chamber, Allergy Center Vienna West, Austria
SIT with HDM allergen extracts is often not effective.
We performed a retrospective blinded analysis of sera from hundred HDM allergic patients who
had been treated with a HDM allergoid extract (n=52) or with placebo (n=48) for 51 weeks
regarding IgE- and IgG-reactivity to a broad panel of micro-arrayed HDM allergens (nDer p
1, rDer p 2, rDer p 5, rDer p 7, rDer p 10, rDer p 11, rDer p 14, rDer p 15, rDer p 18, rDer p
21 and rDer p 23). Sera obtained before (week 0), during (week 23) and after SIT (week 51)
were analyzed for allergen-specific IgE- and IgG-reactivity.
Besides Der p 1 (77.9%) and Der p 2 (93.9%), patients frequently have IgE against Der p 4
(52.0%), Der p 5 (60.9%), Der p 7 (43.5%), Der p 21 (44.7%) and Der p 23 (78.8%). During
the course of SIT, only Der p 1- and Der p 2-specific IgG levels increased significantly in the
verum group whereas for all other tested allergens no induction of specific IgG antibodies
was observed, indicating that the vaccine lacked these allergens in an immunologically active
form. Interestingly, the assessment of clinical efficacy based on registration of the total nasal
symptom scores (TNSS) of the patients determined by allergen exposure in an allergen
exposure chamber before, during and after treatment showed that only patients sensitized
exclusively to Der p 1 and/or Der p 2 showed a significant reduction of TNSS as compared
to the placebo group, whereas patients sensitized also to other HDM allergens showed no
significant improvement.
Our results thus demonstrate that failure of SIT with HDM extracts can be due to lack of HDM
allergens in therapeutic vaccines capable of inducing specific IgG responses.
Contact / E-Mail:
[email protected]
- 56 -
Signaling capacities of the IL-31 receptor complex
University of Salzburg, Department of Molecular Biology, Hellbrunnerstraße 34, 5020 Salzburg
Oral Presentation
Interleukin (IL-) 31 is a member of the IL-6 cytokine family. The human IL-31 receptor
complex consists of OSMR-beta and the IL-31 receptor alpha (IL-31RA), of which five validated
splice variants (two short and three long isoforms) are known. Compared to the short isoforms,
the three long isoforms possess several tyrosine residues for STAT activation. To analyze
the signaling capabilities of all IL-31RA isoforms, we cloned and transfected them into the
human cell lines HeLa, HEK293 and Hep3B, all of which differ in their endogenous OSMR-beta
expression. Reportergene-assays and Western Blotting in HeLa cells showed a dose-dependent
STAT3 activation upon induction with IL-31. Similar experiments in the two other cell lines
showed that co-expression of the second receptor chain OSMR-beta is essentially required for
functional IL-31 receptor signaling. To identify the specific tyrosine residues responsible for
signal transduction we introduced amino acid exchanges into the OSMR-beta chain. In addition,
we identified the essential amino acids for JAK-binding and functional IL-31R signaling. Taken
together, this study shows that long as well as short isoforms of human IL-31RA are capable of
inducing STAT signaling. However direct interaction with OSMR-beta is required.
Abstract 28
Michaela MITTERMEIR, Elisabeth MAIER, Stefanie ESS, Albert DUSCHL, Jutta HOREJS-HOECK
Acknowledgements
This study is supported by the Austrian Science Fund, FWF, grant number P23933.
Contact / E-Mail:
[email protected]
- 57 -
Oral Presentation
Abstract 29
Bidirectional polarization of T cell function via CD43
Madhura MODAK, Petra CEJKA, Petra WAIDHOFER-SÖLLNER, Sabrina JUTZ, Otto MAJDIC,
Peter STEINBERGER, Gerhard ZLABINGER, Johannes STÖCKL
Institute of Immunology, Medical University of Vienna, Vienna, Austria
CD43 is one of the abundant glycoproteins expressed on T cells. CD43 has been demonstrated
to act as not only a potent co-receptor but also a negative regulator for T cell activation. To
further investigate the role of CD43 in T cell activation and subsequent function, peripheral
blood T cells were activated via two distinct CD43 epitopes recognized by monoclonal
antibodies (mAbs) namely 6E5 and 10G7 along with TCR signaling. Both the CD43 mAbs
were shown to be potent co-stimulators for T cell activation when cross-linked but they exert
differential downstream effect upon ligation including differential activation of downstream
signaling pathways, T cell cytokine production and also distinct effector function. T cells
activated via 10G7 mAb were poorly restimulated and further acquired suppressive function
compared to T cells activated either via 6E5 or via CD28. Thus, identifying a novel pathway
to induce immune inhibitory T cells. Furthermore, inhibitory T cells do not directly act on
responder T cells, but rather exhibit their effect via dendritic cells when added to allogenic
mixed leukocyte reaction. Together our data suggests a unique role of CD43 in bidirectional
polarization of T cells immunity, depending on its targeted epitope.
Acknowledgements
The authors would like to thank Claus Wenhardt for his expert technical assistance
Contact / E-Mail:
[email protected]
- 58 -
L. PANGRAZZI, B. Jenewein, J. Lair, M. Krismer, B. Weinberger, B. GrubeckLoebenstein
Institute for Biomedical Aging Research, University of Innsbruck
Oral Presentation
It is well understood that aging leads to a decline of immune function, a process known as
immunosenescence. Latent infection with cytomegalovirus (CMV) may still aggravate the
condition. For this reason it is very important to find new strategies to counteract the problem,
in particular through the maintenance of immunological memory. During the last years, it has
been demonstrated that memory T cells and plasma cells survive in bone marrow niches, well
organized structures which support the homeostatic proliferation of these cells. Plasma cells
home to CXCL-12+/-, CD4+ memory T cells to IL7+ collagen XI+/- and CD8+ memory T cells
to IL-15+ bone marrow cells. CD4+ memory T cell and plasma cell niches have already been
described in mice but not in humans and there is still relatively little information on CD8+ T
cell niches in either species. Our group has demonstrated that, during aging, there is a decline
of naïve and an accumulation of effector memory CD8+ T cells, which are maintained by IL15 producing cells. Moreover, the numbers of plasma cells, which home to CXCL-12+ stromal
cells, decrease in the bone marrow with aging. The aim of this study is to characterize the
bone marrow niches responsible for the maintenance of CD8+, CD4+ memory T cells and
plasma cells and to investigate how they are changing with aging and CMV infection. qPCR
experiments revealed that IL-15 mRNA increased both with age and CMV infection, while IL-7
expression is reduced during aging but not affected by CMV. Immunofluorescence staining of
tissue sections and FACS analysis of cell suspensions were performed to confirm results at the
protein level. We conclude that changes in the bone marrow niches and chronic CMV infection
may lead to decreased antibody responses in elderly.
Abstract 30
Memory T cells and plasma cells niches in human
bone marrow
Contact / E-Mail:
[email protected]
- 59 -
Oral Presentation
Abstract 31
The urokinase receptor as a positive regulator of T
cell activation
Alexander ZWIRZITZ(1), Karin PFISTERER(1), Vladimir LEKSA(2) and Hannes STOCKINGER(1)
(1) Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and
Immunology, Medical University of Vienna
(2) Laboratory of Molecular Immunology, Institute of Molecular Biology, Academy of Sciences,
Bratislava, Slovak Republic
T cell activation and migration of T cells are two central processes in adaptive immunity. We
are interested in one particular molecule namely CD87 (urokinase receptor, uPAR), which
seems to equip T cells with features important in both of them. CD87 is widely recognized
as an important mediator of fibrinolysis and extracellular matrix degradation. Commonly it is
hardly found on resting lymphocytes. However, it has already been shown that T cells start
to express CD87 upon activation (Nykjaer et al 1994). Furthermore, there is evidence that
CD87 is important in lymphocyte migration to sites of infection (Gyetko et al 2001). Yet,
detailed mechanisms as well as CD87s role in other aspects apart from migration have so far
not been investigated. We therefore examine CD87s function in T cell activation and migration
in more detail. We observed that T cells overexpressing CD87 change their phenotype from
suspension to adherent cells. In addition, these cells display an elevated response to T cell
receptor stimulation as measured by calcium mobilization and IL-2 production. In our current
experiments we want to clarify functional consequences of CD87 expression on T cells, dissect
CD87s signaling pathways and elucidate the molecular mechanisms responsible for our
observations.
Contact / E-Mail:
[email protected]
- 60 -
Molecular analysis of MAZR function in CD4+ T cells
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology
and Immunology, Medical University of Vienna, Vienna, Austria
Oral Presentation
Transcriptional and epigenetic mechanisms play a key role in the regulation of T cell
development and function. We identified the BTB zinc finger protein MAZR (also known as
Patz1) as an important regulator of Cd8 gene expression in DN thymocytes and revealed its
essential role in CD4/CD8 lineage choice of DP thymocytes. However, the role of MAZR in
peripheral T cell development has not been elucidated so far. To comprehensively analyze the
in vivo and in vitro role of MAZR in CD4+ T cells, we are employing conditional gene targeting
approaches (using the Cd4-Cre deleter strain) as well as gain-of-function studies using
retroviral-mediated overexpression strategies. Preliminary results suggest a role for MAZR in
modulating Th17/Treg effector differentiation and function. Data from our ongoing experiments
will be presented.
Abstract 32
Liisa ANDERSEN, Alexandra SCHEBESTA, Alexandra GÜLICH, Shinya SAKAGUCHI and Wilfried
ELLMEIER
Acknowledgements
Supported by FWF.
Contact / E-Mail:
[email protected]
- 61 -
Oral Presentation
Abstract 33
Structural and functional rejuvenation of the aged
brain by an approved anti-asthmatic drug
Julia MARSCHALLINGER(1,2), Barbara KLEIN(1,2), Iris Schäffner (3,4), Sébastien COUILLARDDESPRES(2,5), Claudia SCHMUCKERMAIR(6), D. Chichung Lie (3,4), Nicolas SINGEWALD (6),
Ludwig AIGNER(1,2)
(1) Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg,
Austria
(2) Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Salzburg,
(3) Research Group Adult Neurogenesis and Neural Stem Cells, Institute of Developmental
Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health,
Munich-Neuherberg, Germany
(4) Institute of Biochemistry, Emil Fischer Center, Friedrich-Alexander-University ErlangenNürnberg, Erlangen, Germany
(5) Institute of Experimental Neuroregeneration, Paracelsus Medical University, Salzburg,
Austria
(6) Department of Pharmacology and Toxicology, Institute of Pharmacy and CMBI, LeopoldFranzens-University of Innsbruck, Innsbruck, Austria
Leukotrienes, mediators of inflammation, are well-studied in asthma and allergy, and
leukotriene receptor antagonists such as the drug montelukast have been successfully
developed to treat asthmatic patients. In the aged brain, elevated levels of leukotrienes might
be involved in neuroinflammation and in age-related cognitive impairments, as well as in
reduced adult neurogenesis, since we demonstrated that montelukast induced a significant
increase in neuronal progenitor proliferation in vitro.
Here, we tested if a 6-week oral montelukast (10 mg kg-1) treatment of young (4 months)
and aged (20 months) rats has beneficial effects on cognition, and analyzed potential modes
of action including neuroinflammation, blood-brain barrier integrity, neuronal activity, and
hippocampal neurogenesis. To gain information on the role of the putative leukotriene receptor
GPR17, we analyzed the impact of montelukast on adult FoxO deleted neurospheres, which
show strongly reduced GPR17 expression.
We showed that montelukast promotes neurogenesis, decreases neuroinflammation and
restores blood-brain barrier specifically in aged rats. Most intriguingly, this already marketed
anti-asthmatic drug, acting on leukotriene receptors, restored cognitive functions in aged rats.
Contact / E-Mail:
[email protected]
- 62 -
- 63 -
Poster Presentation
Abstract 34
Identification of linear and conformational epitopes
of bovine alpha -lactalbumin
Yuan SHUILIN (1,2), Li XIN(1,2), Chen HONGBIN(1,2), Gao JINYAN(1,2), Wu ZHIHUA(1,2),
Yang ANSHU(1,2), Tong PING(1,2)
(1) State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang
330047, P.R. China
(2) Department of life sciences and food engineering Nanchang University, Nanchang 330047,
P.R. China
Background: Alpha-lactalbumin (ALA) is one of the major allergens in cow milk. However, the
research on its epitopes was relatively limited, especially for conformational epitopes.
Methods: Patient’s sera specific for cow’s milk ALA were purified by affinity chromatography
and then mimotopes against IgG and IgE was obtained by the biopanning of the Ph.D.-C7C and
Ph.D.-12 phage display library, respectively. On the basis of mimotopes, continuous epitopes
were defined using the mimic peptide frequency from Alignment UniProt and conformational
epitopes were computed using Web service of Pepitope Server.
Results: IgE linear epitopes were located in AA41-46, AA55-60, AA62-72, AA74-76, AA85-90
and AA92-99,while position of IgG linear epitopes were AA37-46, AA52-54, AA56-59, AA63-72,
AA74-76, AA81-90 and AA92-99, respectively. Five IgE and three IgG conformational epitopes
were rendered with PyMOL.
Conclusions: It is first time to identify conformational epitopes of ALA. Some common
residues appeared in linear and conformational epitopes , which provided a diagnostic tool
giving information on the cow’s milk patients. This study indicated that many conformational
epitopes were composed linear epitopes.
Acknowledgements
The work was supported by National High Technology Research and Development Program of
China (863 Program, No. 2013AA102205), National Natural Science Foundation of China (No.
31260204 and 31301522)
Contact / E-Mail:
[email protected]
- 64 -
Viktoriya GARIB (1), Eva WOLLMANN (1), Gulnara DJAMBEKOVA (2), Rudolf VALENTA (1)
(1) Division of Immunopathology, Department of Pathophysiology and Allergy Research,Center
of Pathophysiology, Infectiology and Immunology, Medical University of Vienna
(2) Specialized Scientific-Practical Center for Therapy and Medical Rehabilitation (RSSPMC T&R),
Tashkent, Uzbekistan
Poster Presentation
The green zones in Tashkent-city in Uzbekistan have been re-organized during the last 2
decades. Covering approximately 35% of the city´s surface, it includes vegetation commonly
present in Central Asia such as saltwort and newly planted species like Bermuda grass.
Determination of the molecular sensitization profiles of allergic patients is essential for the
correct treatment with allergen specific immunotherapy but has not been established for
allergic patients in the Central Asian area.
The aim of this study was to determine the IgE-sensitization profile towards pollen allergens in
patients with respiratory allergy from Tashkent in dynamic to new landscape.
Sera of fifty adult patients with allergic rhinitis and/or asthma were analyzed using an allergen
micro-array containing 112 different allergen molecules (ImmunoCAP ISAC; Thermo Scientific).
42/50 showed pollen associated allergic symptoms. We separated them into 3 groups
according to their age (middle aged adults-1: MAA-1 (30-39 years), middle aged adults-2
MAA-2 (40-49 years), young adults YA (20-29 years)).
We found that 78,7% of patients with respiratory allergy were polysensitized. The hierarchy
of pollen sensitization is: nSal k 1 (54,7%) > nCyn d 1 (50%) > rPhl p 1 (38,1%) >
nPla a2 (26,1%) > rPla l 1 (23,8%) > rPhl p 5 (21,4%). No IgE reactivity was observed
towards rAln g 1, rBet v 1, rBet v 4, rCor a 1.001.01, rPar j 2, and rPhl p 11. The pattern of
genuine sensitization “grass-weed-tree” appears with the highest frequency. A difference in
the frequency of IgE sensitization could be detected in different age groups. A decrease of
sensitization rates against nSal k 1 from 83,3% in the middle-aged adults to 30% in younger
patients , and against rPla a 1 from 25% to 5% could be detected. On the other hand the
number of young allergics with IgE against nCup a 1 is 4,8x greater than the number in the
elder group with similar sensitization. Our data show the predominant role of nCyn d 1 in the
Uzbek population as the most frequently detected allergen in all age groups.
The results of the IgE profiling identified grass pollen and in particular Bermuda grass and
salkwort as the most important pollen allergen sources in Tashkent and a variation in these
results is observable upon implementation of environmental changes. These data show that
the molecular sensitization profile towards pollen allergens in Central Asia is a consequence of
the local flora and its alterations indicate the importance of allergen micro-array analysis for
the selection of the correct immunotherapy treatment.
Abstract 35
In-print of the environment on the molecular
sensitization profile towards pollen allergens
revealed by allergen micro-array.
Acknowledgements
This study was supported by the Austrian Science Fund (FWF; DK: Inflammation and
Immunity), American Austrian Foundation (AAF) and was performed within the framework of
the International Network of Universities for Molecular Allergology and Immunology.
Contact / E-Mail:
[email protected]
- 65 -
Poster Presentation
Abstract 36
Characterization of recombinant gamma-gliadin
protein and its evaluation for diagnosis of wheat
hypersensitivities
Bharani Srinivasan1, Margarete Focke-Tejkl1, 2, Milena Weber1, Sandra Pahr1, Alexandra
Baar1, Michael Hertl3 , Raja Atreya4, Markus.F.Neurath4, Harald Vogelsang5, Wolf-Dietrich
Huber6, Rudolf Valenta1, 2
for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
(2) Christian Doppler Laboratory for Allergy Research, Medical University of Vienna, Vienna,
Austria
(3) Departments of Dermatology and Allergology, Philipps University Marburg, Marburg,
Germany
(4) Medical Clinic 1, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
(5) Department of Gastroenterology and Hepatology, Medical University of Vienna, Vienna,
Austria
(6) Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna,
Austria
Celiac disease (CD) and dermatitis herpetiformis (DH) is caused by hypersensitive immune
reaction to gliadins, but these proteins are poorly characterized. Our aim was to characterize
gamma-gliadin (GG1) identified from CD-specific gliadin sub-fraction and to study its
usefulness for diagnosis of wheat hypersensitivities and monitoring diet adherence. Methods:
GG1 was recombinantly expressed and characterized biochemically and structurally.
Immunological characterization was performed using CD, DH and control subject’s sera.
IgA- and IgG-epitopes were identified using overlapping peptides. GG1 and peptide-specific
antibodies were raised for tracing GG1 in cereals, wheat products and to study its resistance to
digestion. Results: rGG1 is unfolded and oligomeric. IgA-reactivity to rGG1 is a specific marker
for CD, DH and useful for monitoring diet adherence by CD patients. Peptide 4 from Pro/Glnrich domain was the immunodominant epitope. GG1-related antigens were found in closely
related but not in unrelated cereals. GG1 was detected in wheat products after baking and,
the major IgA epitope containing region was resistant to digestion. Conclusions: rGG1 and its
peptides may be useful for diagnosis, follow-up, understanding disease mechanism, prevention
and therapy.
Acknowledgements
This study was supported by the FWF-funded PhD program IAI and by the Medical University of
Vienna and in part by a research grant from Phadia/Thermofisher Scientific, Uppsala, Sweden.
Contact / E-Mail:
[email protected]
- 66 -
Sheron DZORO, Irene MITTERMANN, Rudolf VALENTA
Department of Pathophysiology and Allergy Research,Medical University of Vienna, ViennaAustria
Poster Presentation
We have found that approximately 30% of patients suffering from atopic dermatitis (AD)
displayed IgE reactivity against a variety of antigens from E. coli. This finding is unusual
because E. coli is known as a natural, tolerogenic constituent of the human microbiome, and
exposure to bacteria has been reported to have anti-allergenic activity in various studies.
Therefore as a first step, we have investigated by IgE inhibition experiments whether IgE
reactivity to E. coli antigens is due to cross-reactivity with Staphyloccocus aureus or Malassezia
sympodialis, which are frequent skin pathogens in AD. However, no evidence for relevant
cross-reactivity was obtained. In order to identify genuine IgE-reactive components of E. coli,
a commensal strain ATCC25922 was selected for investigation.
Abstract 37
Construction of a phage display library from
Escherichia coli to study IgE-reactive bacterial
antigens.
E. coli total genomic DNA was extracted and randomly fragmented by enzymatic restriction.
Generated DNA fragments were ligated into a plasmid vector and plasmids with inserts were
selected for amplification. Polymerase chain reaction was performed across the cloning region
of the vector, to check nucleotide sequences of the inserts. Upon BLAST analysis, sequences
of various constituents of E.coli were identified in the library, including transcription factors,
chaperone and transporter proteins, isomerase enzymes and putative membrane proteins.
The constructed library will now be screened by biopanning procedures, to identify IgE binding
clones.
Contact / E-Mail:
[email protected]
- 67 -
Poster Presentation
Abstract 38
The immune response against the timothy grass
pollen allergen Phl p 5 in non-allergic humans
depending on different environments
Almedina ISAKOVIC, Christoph HILLEBRAND, Theresa THALHAMER, Sandra SCHEIBLHOFER,
Josef THALHAMER, Richard WEISS
University of Salzburg, Department of Molecular Biology, Division of Allergy and Immunology,
Hellbrunnerstraße 34, 5020 Salzburg
The “hygiene hypothesis” states that a lack of exposure to microbial components during
early childhood leads to a higher risk to develop allergic diseases, whereas a high diversity
of microbes could be crucial for the establishment of a non-allergic immune system. In this
study, we assess the immune status of non-allergic people living in a farming envorinment,
who are regularly exposed to timothy grass pollen allergen in the context of a diverse microbial
environment. And in addition non-allergic people living in an urban environment, who lack such
microbial exposure. PBMCS from non-allergic donors are expanded antigen-specifically with
Phl p 5. Expression of surface markers and transcription factors, as well as cytokine secretion
allows identification of TH1, TH2, Treg and TH17 cells. Moreover, IgE, IgG1 and IgG4 antibody
levels in non-allergic human plasma are measured. We found a high phenotypic diversity
among non-allergic individuals, indicating that multiple mechanisms of naturally acquired
protection exist. These established methods will allow to statistically assess the distribution
of different T-cell subsets in the non-allergic immune system, depending on different
environments and to find a potential link between exposures to microbes and the development
of allergy.
Contact / E-Mail:
[email protected]
- 68 -
Stephanie EICHHORN(1), Isabel PABLOS(1), Serge VERSTEEG(2), Laurian ZUIDMEERJONGEJAN(2), Ronald VAN REE(2), Fatima FERREIRA(1), Gabriele GADERMAIER(1)
(1) University of Salzburg, Department of Molecular Biology, Division of Allergy and
Immunology, Salzburg, Austria
(2) Department of Experimental Immunology, Academic Medical Center, Amsterdam, The
Netherlands
Poster Presentation
The influence of molecular properties on adjuvant binding and the immunologic behavior was
evaluated by comparing rPru p 3 C1 (C1), a potential hypoallergenic vaccine candidate against
peach allergy and the wild-type rPru p 3 (WT).
Analysis by circular dichroism spectroscopy, dynamic light scattering, and size-exclusion
chromatography, showed a compact, alpha-helical fold for the WT protein whereas C1 adopted
a loosened, random-coil conformation. Due to more accessible surface charges, binding of C1
to two different adjuvants (aluminum hydroxide, and aluminum phosphate) was enhanced
compared to WT in in vitro experiments. In contrast to WT, C1 demonstrated a very high
susceptibility to endolysosomal proteolysis. After immunizing Balb/c mice (n = 6) using
adjuvant adsorbed proteins, the WT protein elicited a robust antibody response regardless of
the formulation. Aluminum phosphate adsorbed C1 triggered an immune response in all mice
(50% cross-reactive with WT), while aluminum hydroxide induced IgG in only one mouse.
It could be demonstrated that adjuvants’ formulation, adsorption rate and endolysosomal
stability influence the immunologic profile. These variables should be taken into account when
designing and administering protein vaccines.
Abstract 39
Immunogenicity of the major peach allergen
Pru p 3: Does protein conformation,
physico-chemical properties and stability matter?
Acknowledgements
The study was supported by the FAST project EU grant 201871.
Contact / E-Mail:
[email protected]
- 69 -
Poster Presentation
Abstract 40
ImmunoCAP cellulose displays cross-reactive
carbohydrate epitopes and can cause false-positive
test results in patients with anti-CCD IgE antibodies
Wolfgang HEMMER(1), Stefan WÖHRL(1), Felix WANTKE(1), Friedrich ALTMANN(2)
(1) Floridsdorf Allergy Center, Vienna, Austria, (2) Department of Chemistry, University of
Natural Resources and Life Sciences, Vienna (BOKU), Austria
Rationale: CCDs in plant and insect venom extracts may cause false-positive in vitro test
results. We noticed that some CCD-positive sera show multiple positive ImmunoCAP results
even with CCD-free recombinant allergens.
Methods: IgE-binding to recombinant allergens and to allergen-free blank ImmunoCAPs (BIC)
was compared in CCD-positive sera before and after CCD inhibition.
Results: 35/52 (67%) CCD-positive sera (bromelain 1.01-59.6 kU/l) reacted with BIC ≥0.35
kU/l (0.35-4.22 kU/l). IgE-binding to BIC correlated with binding to bromelain (r=0.80) and
was completely abolished by a CCD inhibitor. Binding to another five lots of BICs was lower but
correlated strongly with the first lot (r≥0.94). Of 10 CCD-reactive sera (14.0-52.5 kU/l) tested
on recombinant Phl p12, Fel d 1, Ara h 2, and Pru p 3, 8 were positive to all components (0.361.6 kU/l), 2/10 showed borderline results. Binding to components correlated with binding to
bromelain (r=0.61) and BIC (r=0.97) and was completely blocked by CCDs. MS confirmed the
presence of MMXF glycans in unprocessed and processed cellulose.
Conclusions: The ImmunoCAP cellulose allergen carrier contains varying traces of CCDs and
can cause false-positive results to non-glycosylated allergens in patients with high levels of
anti-CCD IgE antibodies.
Contact / E-Mail:
[email protected]
- 70 -
Sabrina WILDNER(1,2), Lorenz STOCK(2,3), Adriano MARI(4), Hanno STUTZ(2,3) and Gabriele
GADERMAIER(1,2)
(2) Christian Doppler Laboratory for Innovative Tools for the Characterization of Biosimilars,
Salzburg, Austria
(3) University of Salzburg, Department of Molecular Biology, Division of Chemistry and
Bioanalytics, Salzburg, Austria
(4) Associated Centers for Molecular Allergology, Rome, Italy
Poster Presentation
Artemisia vulgaris (mugwort) is an important elicitor of pollinosis in late summer and autumn.
The structural and immunological behavior of Art v 3, the non-specific lipid transfer protein
(LTP) upon thermal treatment was investigated. Recombinant Art v 3.0201 was produced in
E. coli and purified using CEX. The molecule was heated up to 120 min at 95°C in acidic (pH
3.4) and neutral (pH 7.3) buffers. Circular dichroism showed high thermal stability at pH 3.4
while the alpha helical fold was lost upon 15 min heating at pH 7.3. Conformational changes
were investigated by capillary electrophoresis hyphenated to time-of-flight mass spectrometer
indicating a decay of disulfide bonds by beta elimination and formation of lanthionine(s).
Native Art v 3 is monomeric presenting a hydrodynamic radius of 1.8 nm. Relaxing of the
compact shape is observed upon heat treatment at pH 7.3 which is not attributed to protein
aggregation as determined by SEC. Notably, IgE reactivity to Art v 3 was completely reduced
upon heating at pH 7.3 but remained largely unaffected at pH 3.4 suggesting involvement of
conformational epitopes. Susceptibility of Art v 3 to thermal treatment is highly dependent on
ambient conditions and thus studies enrolling pollen and food derived LTPs should consider
these facts.
Abstract 41
Investigation of the structural and immunological
behavior of Art v 3 upon thermal treatment
Acknowledgements
The financial support by the Austrian Federal Ministry of Science, Research and Economy and
the National Foundation of Research, Technology and Development is gratefully acknowledged.
Contact / E-Mail:
[email protected]
- 71 -
Poster Presentation
Abstract 42
Characterization and IgE epitope mapping of Tri
a 37, a serological marker for severe wheat food
allergy
Sandra PAHR(1,2), Regina SELB(3), Claudia CONSTANTIN(1), Milena WEBER(1), Margit
FOCKE-TEIJKL(1), Gerhard HOFER(4), Andela DORDIC(4), Walter KELLER(4), Nikolaos G.
PAPADOPOULOS(5), Stavroula GIAVI(5), Mika MÄKELÄ(6), Anna PELKONEN(6), Verena
NIEDERBERGER(3), Susanne VRTALA(1,2), Rudolf VALENTA(1)
of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
(2) Christian Doppler Laboratory for the Development of Allergen Chips, Medical University of
Vienna, Vienna, Austria
(3) Department of ENT, Medical University of Vienna, Vienna, Austria
(4) Institute of Molecular Biosciences, Karl-Franzens University Graz, Graz, Austria
(5) Allergy Department, 2nd Pediatric Clinic, University of Athens, Athens, Greece
(6) Skin and Allergy Hospital, Helsinki University Central Hospital, Helsinki, Finland
Wheat is an important staple food that can cause IgE-mediated food allergy. Recently, we
identified Tri a 37 as a marker allergen for severe allergic reactions in wheat food allergic
patients. The purpose of the present study was the recombinant expression of Tri a 37 in two
different expression systems and their characterization regarding molecular, structural and
immunological properties. Furthermore, we aimed to characterize relevant epitopes of Tri a 37.
Recombinant Tri a 37 was expressed in a prokaryotic expression system using E.coli cells
and in a eukaryotic expression system using baculovirus-infected insect cells, purified to
homogeneity and characterized by means of SDS-PAGE, mass spectrometry, circular dichroism,
chemical crosslinking and non-denaturing RAST-based binding assays. Five overlapping
peptides were synthesized and used for epitope mapping. Tri a 37-specific rabbit antibodies
were raised to perform inhibition experiments and to study its resistance to digestion.
Tri a 37 expressed in the prokaryotic system was unfolded whereas using the eukaryotic
expression system, we obtained an α-helically folded protein. In non-denaturing RAST-based
experiments, both allergens showed comparable IgE-reactivity. IgE and IgG epitope mapping
using synthetic peptides revealed that Tri a 37 contains sequential epitopes.
Since major IgE epitopes of Tri a 37 are sequential epitopes, Tri a 37 is a true wheat food
allergen that can be used for the ín-vitro diagnosis of severe wheat food allergy.
Contact / E-Mail:
[email protected]
- 72 -
Lorenz AGLAS(1), Claudia ASAM(1), Stefanie GILLES(2), Claudia TRAIDL-HOFFMANN(2),
Fatima FERREIRA(1), Michael WALLNER(1)
(1) Department of Molecular Biology, University of Salzburg, Austria
(2) Institute of Environmental Medicine, UNIKA-T, Klinikum rechts der Isar, Technische
Universität München, Germany
Poster Presentation
Birch pollen allergy is one of the most prevalent allergies in Europe. More than 95% of
birch pollen allergic patients are sensitized to Bet v 1, the major allergen of birch pollen.
Structurally, Bet v 1 is a globular protein and has the ability to bind a variety of ligands within
its hydrophobic cavity.
The impact of ligand binding on the immunogenic and allergenic properties of Bet v 1.0101
(called Bet v 1 in the following) is still a matter of discussion. Therefore, we investigated the
intrinsic ligand binding properties of recombinant Bet v 1.
In this respect we used a selection of different ligands. Extrinsic fluorescence studies with ANS
(8-anilinonaphthalene-1-sulfonic acid) were used to demonstrate the interaction of the protein
with the ligands. Furthermore, the thermal and proteolytic stability was determined in the
presence and absence of a ligand.
Protein-ligand interactions were verified for each ligand. In terms of thermal and proteolytic
stability, some ligands appeared to have a stabilizing effect, as observed for sodium
deoxycholate, whereas others did not.
Ligand binding appears to influence the structural properties of Bet v 1. It is possible that the
stabilizing effect of a ligand may be a crucial characteristic of Bet v 1 during the sensitization
process.
Abstract 43
Analysis of interactions of the major birch pollen
allergen Bet v 1 with naturally occurring and
synthetic ligands
Contact / E-Mail:
[email protected]
- 73 -
Poster Presentation
Abstract 44
Structural and immunological study of allergenic
defensin-like proteins from mugwort, ragweed and
feverfew
Isabel PABLOS(1), Stephanie EICHHORN(1), Yoan MACHADO(1),Peter BRIZA(1), Christof
EBNER(2), Naveen ARORA(3), Stefan VIETHS(4), Gabriele GADERMAIER(1), Fatima
FERREIRA(1)
(1)University of Salzburg, Department of Molecular Biology, Division of Allergy and
(2)Allergy Clinic Reumannplatz, Vienna, Austria
(3)CSIR-Institute of Genomic and Integrative Biology, Allergy and Immunology Section, Delhi,
India
(4)Paul-Ehrlich-Institut, Division of Allergology, Langen, Germany
Defensin-like proteins, Art v 1, Amb a 4 and Par h 1 are relevant allergens from mugwort,
ragweed and feverfew pollen. Beyond sequence similarities and allergenicity, little is known
about the structural and immunological features shared by these proteins. Thus, we aimed
to produce the recombinant allergens for comprehensive physicochemical and immunological
studies. For the first time the Par h 1 coding region including the signal peptide was identified
from total RNA using a degenerated primer followed by 5’-RACE protocol. The recombinant
proteins Art v 1.0101, Amb a 4.0101 and Par h 1 were expressed as non-fusion soluble
proteins in E. coli Rosetta-gamiB pLysS. Purity of >95% was assessed by gel electrophoresis
and mass spectrometry. Mass analysis confirmed protein identities. Circular dichroism and
Fourier transform infrared spectroscopy analysis revealed similar foldings for Art v 1, Amb a 4
and Par h 1. The three allergens showed different stability to endolysosomal degradation. The
analysis of weed sensitized patients’ sera from Austria displayed different sensitization profiles
to Art v 1, Amb a 4 and Par h 1 with partial IgE cross-reactivity. These proteins will enable to
study sensitization and IgE cross-reactivity of defensin-like allergens in large patients’ cohorts.
Acknowledgements
Funded by ERA New INDIGO project I1152.
Immunity in Cancer and Allergy, PhD program-University of Salzburg.
Contact / E-Mail:
[email protected]
- 74 -
Bianca KASTNER(1), Stephanie EICHHORN(1), Isabel PABLOS(1), Sabrina WILDNER(1), Ines
FORSTENLEHNER(2), Stefan VIETHS(3), Naveen ARORA(4), Gabriele GADERMAIER(1), Fatima
FERREIRA(1)
The American cockroach Periplaneta americana is a major source of indoor allergens and
frequently causes allergic reactions and asthma. Per a 1 can be found in the midgut and fecal
excrements; however its function is not known yet. The aim of the study was the recombinant
production, physico-chemical and immunological investigation of the allergen. The second
tandem repeat of Per a 1.0103 (residues 197-378) was cloned in pHIS parallel 2 vector and
expressed as soluble non-fusion protein in E. coli BL21 star. The protein was purified by anion
exchange and size exclusion chromatography with a yield of ~9 mg/L. Purity of >95% was
demonstrated by gel electrophoresis. The identity was confirmed by mass spectrometry and
amino acid analysis. The CD depicted a curve typical for alpha helical proteins with a minimum
at 222 nm. IgE binding was tested in ELISA using sera of 13 cockroach allergic patients. The
purified protein will be used to evaluate IgE sensitization, cross-reactivity and clinical relevance
in large patients’ cohorts from India, Europe and America.
Poster Presentation
(2) University of Salzburg, Department of Molecular Biology, Division of Analytical Chemistry
and Bioanalytics, Salzburg, Austria
(3) Paul-Ehrlich-Institute, Division of Allergology, Langen, Germany
(4) CSIR-Institute of Genomics and Integrative Biology, Allergy and Immunology Section, Delhi,
India
Abstract 45
Production and characterization of recombinant
Per a 1, a major allergen of Periplaneta americana
Acknowledgements
The work was funded by the ERA New INDIGO project I1152.
Contact / E-Mail:
[email protected]
- 75 -
Poster Presentation
Abstract 46
Renaissance of a well-known contact-allergen
Tamar KINACIYAN
DIAID, Department of Dermatology, Medical University of Wien
Background and Objective: We report on two young ladies who came with massive eyelid
eczema and conjunctivitis to our outpatient clinic. The history revealed in one patient that
she had colored her eyebrows one day before the onset of eczema and the other colored her
eyelashes.
Methods: Patch tests with the European standard series and hairdresser materials were
performed. In one patient additionally textile dyes were tested.
Results: In the European standard series was p-Phenylendiamine (PPD) in both patients
positive. In hairdresser materials, one patient reacted positive to p-Toluylendiamine,
p-Aminophenol, 3-Apinophenol the second patient to p-Aminophenol, Hydroquinone and
Dispersions orange.
Conclusions: Re-evaluation of case history in both patients revealed contact dermatitis to
henna-tattoo more than 10 years ago. The second patient developed scars from this contact
dermatitis. Both had not yet consulted any allergist for these reactions and did not know that
in all cases the causative substance was PPD. Thus, all henna-tattoo- or PPD-allergic patients
should also be made aware of an allergic reaction to eyelash and eyebrow dyes.
Contact / E-Mail:
[email protected]
- 76 -
Regina FREIER and Hans BRANDSTETTER
Structural Biology Group, Department of Molecular Biology, University Salzburg
Poster Presentation
Proteolytic processing by endolysosomal proteases is a key event in the development of an
allergic response. We investigate the idea that sensitizing allergens (e.g. Bet v 1a) are highly
resistant, and can only be cleaved after endolysosomal proteases induce conformational
changes. This hypothesis is supported by the identification of four initial Bet v 1a processing
sites by cathepsin S (1), which are harbored within secondary structure elements, seemingly
not accessible to proteolytic processing. In contrast, non-sensitizing structural homologues can
easily be cleaved be many proteases.
To study the conformational transition of allergens, crystallization of cathepsin S in complex
with peptides corresponding to the four initial cleavage sites of Bet v 1a is intended. To prevent
peptide cleavage we produced an active site dead mutant of cathepsin S. Interactions with
Bet v 1a peptides in the active site should reveal which amino acids are important for the
recognition. Additionally peptide conformations will allow to model the transition within the
allergen.
The accessibility of sensitizing and non-sensitizing allergens can be further studied by
measuring binding kinetics with surface acoustic technology (SAW). The affinity of cathepsin S
to intact and fragmented Bet v 1a will show if reordering precedes its processing by cathepsin
S. Furthermore the comparison between sensitizing allergens and structural homologues might
reveal the general importance of the recognition by proteases in allergenicity.
Abstract 47
Recognition of birch pollen allergen Bet v 1 by
endolysosomal proteases
(1)
Egger et al. (2011) Assessing Protein Immunogenicity with a Dentritic-Cell Line-Derived
Endolysosomal Degradome In PLoS One
Contact / E-Mail:
[email protected]
- 77 -
Poster Presentation
Abstract 48
Investigation of indoor allergen exposure and IgE
sensitization
Bettina SCHWEIDLER(1), Teresa STEMESEDER(1), Eva KLINGLMAYR(1), Lisa
LÜFTENEGGER(2,3), Stephanie MOSER(4), Roland LANG(2), Martin HIMLY(1), Gertie J.
OOSTINGH(3), Arne BATHKE(5), Jörg ZUMBACH(4), Thomas HAWRANEK(2), Gabriele
GADERMAIER(1)
(1)University of Salzburg, Department of Molecular Biology, Salzburg, Austria
(2)Paracelsus Medical University Salzburg, Department of Dermatology, Salzburg,Austria
(3)Salzburg University of Applied Sciences, Biomedical Sciences, Salzburg, Austria
(4)University of Salzburg, School of Education, Salzburg, Austria
(5)University of Salzburg, Department of Mathematics, Salzburg, Austria
Allergic diseases were considerably increasing during the last decades; the reasons for this
development are however not fully elucidated. The aim of our work is to assess the correlation
between allergen exposition and IgE sensitization. Therefore, 501 school children (13-21
years) living in different geographic areas (urban, rural or alpine) from Austria participated in
our study. Using a fluorescent multiplex array, exposition to indoor allergens from cat, dog,
mites and molds were analyzed using house dust samples. IgE sensitizations to respective
allergens were evaluated by ImmunoCap ISAC. The most prevalent allergens in the house
dust were Fel d 1 and Can f 1, while Alt a 1 amounts were insignificant. Exposition to cat
and dog allergens was higher in houses, while mite allergens were considerably elevated on
farms. Students in alpine regions were less exposed to mites, which translated into lower IgE
sensitization. Fel d 1 exposition was slightly higher in urban areas but did not lead to enhanced
IgE development. Although exposed to equivalent Can f 1 amounts, subjects living in urban
areas showed higher IgE sensitizations. We conclude that IgE sensitization is not generally
associated with allergen exposition but is impacted by environmental and lifestyle factors.
Acknowledgements
The study was funded by Sparkling Science, a program of the Federal Ministry of Science,
Research and Economy, Vienna, Austria.
Contact / E-Mail:
[email protected]
- 78 -
Juan R URREGO(1), João PONTE(1), Michael WALLNER(2), Carina PINHEIRO(1), Neuza
ALCANTâRA-NEVES(1), Peter BRIZA(2), Fátima FERREIRA(2)
(1) Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil
Poster Presentation
Background: Blomia tropicalis is an important source of allergens associated with allergic
asthma in tropical and subtropical regions. However, the clinical importance of group 2
allergens from this mite species is still under debate. Until now only rare information of Blo t 2
is available, most of it obtained at the transcript level.
Methods: Blomia tropicalis extracts were prepared from different breeds collected and cultured
in Bahia, Brazil. Mite extracts were prepare using phosphate buffered saline and proteolytically
digested with a set of distinct proteases. Peptides were analyzed by liquid chromatographymass spectrometry (LC-MS).
Results: By MS analysis we were able to identify all isoforms of Blo t 2 at the proteome
level and quantify their relative abundance. Moreover, we found for the first time that Blo
t 2 is initiated by a signal peptide, which is processed during expression. The cleavage site
determined by MS could be confirmed using the software SignalP 4.0.
Conclusion: We successfully identified and quantified mature Blo t 2 isoforms at the protein
level. This constitutes a crucial step for the selection of candidate molecules for recombinant
production and immunologic characterization of this allergen.
Abstract 49
Proteomic characterization of the Blomia tropicalis
allergen Blo t 2
Contact / E-Mail:
[email protected]
- 79 -
Poster Presentation
Abstract 50
Stability and micro-heterogeneity of Cor a 14, the
2S albumin from hazelnut
Sabine PFEIFER(1), Pawel DUBIELA(1), Merima BUBLIN(1), Karin HUMMEL(2), Christine
HAFNER(1,3), Karin HOFFMANN-SOMMERGRUBER(1)
Austria
(2) VetCore Facility for Research, VetOmics, University of Veterinary Medicine Vienna, Austria
(3) Karl Landsteiner Institute for Dermatological Research, St. Poelten, Austria
Allergens from nuts tend to induce severe allergic reactions in sensitive individuals. 2S
albumins are water-soluble storage proteins sharing a characteristic structure and considered
to be major allergens in many seeds and nuts. The aim of this study was to purify and
characterize natural Cor a 14, the 2S albumin from hazelnut, and to investigate its allergenic
activity.
Cor a 14 was purified from raw hazelnuts, characterized and identified with a sequencecoverage of 100%. We estimated a molecular mass of ~12 kDa which is in accordance with
the mature protein. Further, we could identify two different isoforms and showed microclipping
at the C-terminus. CD spectra at room temperature showed the typical characteristics of 2S
albumins and temperatures of more than 80°C were necessary to start unfolding of Cor a 14
demonstrating its high stability to heat treatment. In vitro digestion experiments, simulating
gastric and duondenal conditions, revealed that Cor a 14 is completely resistant to proteolytic
degradation. Native as well as heat-treated protein was recognized by sera from hazelnut
allergic patients. However, reduction led to reduced IgE binding in more than 60% of tested
sera.
Acknowledgements
Supported by grants SFB F4603 and W1248 (Austrian Science Fund) to K. HoffmannSommergruber and P. Dubiela, respectively.
Contact / E-Mail:
[email protected]
- 80 -
Juergen Brunner(1), Thomas Giner(1), Guenter Weiss(2), Dietmar Fuchs(3)
(1) Department of Pediatrics, Medical University Innsbruck, Austria
(2) INTERNAL MEDICINE
(3) Division of Biological Chemistry, Biocenter, , MEDICAL UNIVERSITY INNSBRUCK,
Innsbruck, Austria
Poster Presentation
Background: Juvenile idiopathic arthritis (JIA) is a relevant autoimmune disease in children.
T cells, B cells, and damage-associated molecular patterns (DAMPS) are involved in the
pathogenesis of the disease. Biomarkers for JIA and its subtypes are not established. Proinflammatory pathways activate enzyme indoleamine 2,3-dioxygenase (IDO) which enhances
tryptophan (Trp) conversion to kynurenine (Kyn). Thus, in conditions of chronic immune
activation reduced Trp availability and production of Kyn and its down-stream metabolites may
inhibit cell proliferation. In rheumatoid arthritis (RA) Trp concentrations are lower in patients
than in controls and the Kyn/Trp ratios are higher and correlate with neopterin concentrations
[1-3].
Abstract 51
Biomarkers of Infallation in juvenile idiopathic
arthritis (JIA)
Objectives: To evaluate Tryptophan as Biomarker in JIA
Methods: In this study, Trp and Kyn metabolism was investigated in children with JIA and
compared to serum neopterin concentrations. Fifty-four sera of 25 JIA patients and 10 samples
of synovial fluid were examined with HPLC (Trp and Kyn) and Elisa (Neopterin, BRAHMS,
Hennigsdorf, Germany). Eighteen sera from 18 children with non-inflammatory diseases were
used as controls.
Results: Trp in the sera of patients was mean 57.2 + SD 19.0 µmol/L and Kyn was mean
2.40 + SD 0.81 µmol/L). Serum neopterin was 5.69 + SD 1.72 nmol/L. In the synovial fluid,
neopterin was mean 10.5 + SD 7.41 nmol/L), Trp was 36.7 + SD 17.4 µmol/L and Kyn was
2.13 + SD 0.75 µmol/L). In control patients, neopterin was 6.93 + SD 3.10), Trp was 57.6 +
SD 14.8) and Kyn was 2.60 + SD 1.60 µmol/L.
Conclusions: Serum Trp concentrations showed no relevant difference in JIA patients vs.
controls. IDO activity reduces Trp primarily in the synovial fluid in JIA patients.
Contact / E-Mail:
[email protected]
- 81 -
Poster Presentation
Abstract 52
The Toll-like receptor 4 agonist MRP8/14 protein
complex (Calprotectin) in autoinflammation:
Potential biomarker in chronic nonbacterial
osteomyelitis – a case report
Jürgen Brunner(1)
Background: The cytoplasmic S100 proteins derived from cells of myeloid origin.
Calprotectin (MRP8/14 protein complex) might be a biomarker either for autoinflammation
and autoimmunopathy. Since autoinflammatory diseases might be a diagnostic challenge
calprotectin may be helpful in the diagnosis of autoinflammatory diseases. Chronic nonbacterial
osteomyelitis (CNO) is an autoinflammatory, noninfectious disease. CNO describes a wide
spectrum from a monofocal bone lesion to the chronic recurring multifocal osteomyelitis
(CRMO). Laboratory and histopathological findings are nonspecific. In some patients systemic
inflammatory signs such as elevated acute phase proteins cannot be found.
Objectives: To test the ability of Calprotectin (MRP8/14 protein complex) serum concentrations
to monitor disease activity in patients with CNO.
Methods: Serum concentrations of Calprotectin (MRP8/14 protein complex) in a patient with
CNO were determined by a sandwich ELISA.
Results: Calprotectin (MRP8/14) level were raised heralding active disease when acute phase
proteins (CrP, erythrocyte sedimentation rate). The calprotectin level was 7872,7 ng/ml
(normal range 0-3000 ng/ml)
Conclusions: Calprotectin (MRP8/14) serum concentrations correlate closely with disease
activity and may herald a flare before clinical manifestation. Therfore MRP8/14 serum
concentrations are a biomarker indicating disease activity in CNO patients.
Contact / E-Mail:
[email protected]
- 82 -
Jürgen Brunner(1), Elisabeth Binder(1), Daniela Karall(1), Johannes Zschocke(2),
Christine Fauth(2)
(2) Department of Human Genetics, Medical University Innsbruck, Austria
Poster Presentation
Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM# 260920) is a rare
autosomal recessive autoinflammatory condition caused by mutations in the MVK gene, which
encodes for mevalonate kinase. There is no standard treatment for HIDS.
Case report:
We report on a 2 year-old Austrian boy with recurrent episodes of fever, febrile seizures,
arthralgias, and splenomegaly. Rash and abdominal pain were also seen occasionally. During
attacks an acute-phase response was detected. Clinical and laboratory improvement was seen
between attacks. These findings led to the tentative diagnosis of HIDS. Sequencing of the
MVK gene showed a homozygous c.1129G>A (p.Val377Ile, also known as V377I) mutation in
the child, while the healthy non-consanguineous parents were heterozygous. The mutation is
known to be associated with HIDS.
Therapy with nonsteroidal anti-inflammatory drugs during attacks had poor benefit. A further
febrile episode resulted in a status epilepticus. Treatment with canakinumab was initiated and
a final dose of 4 mg/kg every 4 weeks resulted in the disappearance of febrile attacks and a
considerable improvement of patient´s quality of life during a 6-month follow-up period. The
drug has been well tolerated, and no side effects were observed.
Conclusion:
Treatment with canakinumab is a therapeutical option for patients with HIDS.
Abstract 53
Interleukin 1 blockade with canakinumab for Hyper
IGD syndrome (HIDS)
Contact / E-Mail:
[email protected]
- 83 -
Poster Presentation
Abstract 54
Complement analysis in patients with Juvenile
Idiopathic Arthritis (WIELISA, SC5b9-ELISA)
T. Giner(1), L. Hackl(1), R. Würzner(2), J. Brunner(1)
(2) Division of Hygiene and Medical Microbiology, Medical University Innsbruck, Austria
The juvenile idiopathic arthritis is a well researched disease in the group of
autoimmunopathies. Beside the deregulation of T-cells and cytokines also the complement
system is involved in the pathogenesis of this group of diseases. This prospective longitudinal
study investigated the contribution of the complement system in patients with juvenile
idiopathic arthritis, using practicable ELISA techniques (Wieslab® screening kit; SC5b9 soluble
terminal complement complex ELISA).
Serum and plasma of the peripheral blood and the synovial fluid were investigated for the
activity of the three complement pathways - classical (CP), mannose binding lectin (MBL),
and the alternative pathway (AP) and total complement activity by measuring SC5b9.
Results where compared to published reference controls and 18 children without activation of
inflammation as an age matched control group.
In total 57 samples of peripheral blood (PB) and 8 samples from synovial fluid (SF) from
28 children with JIA were investigated in a longitudinal observation during acute phase and
remission.
The screening of complement system showed debasement of the AP (8 of 10) and CP (7 of
10) in patients during acute phase (7 of 10). The SC5b9 measurement showed a significant
(p<0.002) higher amount in plasma (3,6AU/ml in median) and serum (31,4AU/ml) during
acute phase compared to the control group (serum - 7,72AU/ml and plasma – 1,25AU/ml in
median).
In conclusion the study confirmed, that the CP and AP of the complement system are main
contributors in the pathogenesis of JIA. Because of significant elevation of SC5b9 in acute
phase of JIA, complement blockade with Anti-C5 may be a therapeutically option in the future.
Contact / E-Mail:
[email protected]
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Reinhard WÜRZNER(1), Tom Eirik MOLLNES(2), Francesco TEDESCO(3), Peter GARRED(4),
Lennart TRUEDSSON(5), Malcolm W. TURNER(6), Moh R. DAHA(7), Robert B. SIM(8)
An ELISA-based kit was introduced about a decade ago with the primary aim to screen for
deficiencies in components of the complement (C) system (WIESLAB® Complement system
Screen). The assay is based on specific and separate analysis of the classical, lectin and
alternative pathway, respectively, using the common terminal end product C5b-9 as surrogate
for hemolysis. This assay is particularly useful for detecting genetic C deficiencies and has
helped to identify the cause of several severe and recurrent infections, renal diseases and
systemic autoimmune diseases. Its use has confirmed the higher sensitivity and specificity
compared to the “antique” hemolytic assays. In particular, this assay detects properdin
deficiencies, which are not always detected in hemolytic assays. Its advantage is to assess
the functionality of all three C pathways independently of biologically variable reagents.
After ten years of clinical use, this assay has now extended its applications to quantitate the
functionality of the C pathways in disease monitoring. New features of this assay include the
use of different dilutions when testing C deficient sera, the assessment of C activation in HUS
samples during acute phase or remission, and its usefulness to monitor patients undergoing C
inhibitor therapy.
Poster Presentation
(1)Division of Hygiene & Med. Microbiology, Innsbruck Medical University, Austria
(2)Department of Immunology, Oslo University Hospital and University of Oslo, Norway
(3)Department of Life Sciences, University of Trieste, Italy
(4)Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet,
University of Copenhagen, Denmark
(5)Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology,
Lund University, Sweden
(6)Immunobiology Unit, Institute of Child Health, University College London, UK
(7)Leiden University Medical Centre, The Netherlands
(8)Pharmacology Department, Oxford University, UK
Abstract 55
Functional analyses of total complement activity in an
ELISA-based kit which replaces haemolytic assays: a
decade of experience and future perspectives
Contact / E-Mail:
[email protected]
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Poster Presentation
Abstract 56
Reactive oxygen species mediated regulation of
linker for activation of T cells in autoimmunity
Florian FORSTER(1), Clara MARQUINA(1), Bernhard MALISSEN(2), Rikard HOLMDAHL(1)
(1) Medical Inflammation Research, Medical Biochemistry and Biophysics, Karolinska Institutet,
Stockholm, Sweden
(2) Centre d’Immunologie de Marseille-Luminy, Université de la Méditerranée, Case 906,
Institut National de la Santé et de la Recherche Médicale, U631, Centre National de la
Recherche Scientifique, UMR6102, 13288 Marseille, France
Linker for activation of T cells (LAT) is a membrane adapter protein necessary for T cell
development and signaling. In human arthritic synovial fluid lymphocytes, oxidative stress has
been suggested to delocalize LAT into the cytosol, leading to unresponsive T cells.
To test the consequences of oxidation on LAT, we created a mouse strain expressing LAT
with cysteine to serine mutations at position 120/172. In vitro experiments revealed no
differences in T cell activation, pointing to no cell intrinsic consequences of the mutation. In
vivo we monitored a minor defect in the development of T cells at the transition from the
double negative to the double positive state. In the periphery we show a reduced expression
of CD62L. In addition we observe a higher inflammation in mice carrying the LAT mutation in a
DTH model.
To further investigate the consequences of LAT oxidation, we crossed the LAT C120/172S
mice with mice showing defective NOX2 dependent ROS production due to a mutation in the
Ncf1 gene. We tested the consequence of LAT mutation in ROS sufficient and deficient mice
in the context of collagen induced arthritis. Surprisingly we didn’t see a difference in the ROS
sufficient mouse, whereas we observed a protection of the LAT mutated mouse in the ROS
deficient setting.
Contact / E-Mail:
[email protected]
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Anna BATYROVA, Irina KONDRAKHINA, Olga KOZHEVNIKOVA, Anna GEVORKYAN
Federal State Budgetary Scientific Institution “Scientific Centre of Children Health”
Poster Presentation
Markers of antiphospholipid syndrome (APS) such as cardiolipin and betta-2 glycoprotein I
IgM, IgG antibodies are often associated with increased risk of thrombus formation at various
diseases. But it has been rare studied in pediatric practice.
Aim: to estimate the cardiolipin and betta-2 glycoprotein I IgM, IgG levels diagnostic
significance in children with suspicion of antiphospholipid syndrome (APS) from different
departments. Methods: the sera of 105 children (2-16 years) were tested on ImmunoCAP.
Results: 62.9% children from rheumatology, 17.1% - gastroenterology, 9.5% neuropsychiatric, 8.6% - nephrology, 1, 9% - cardiology departments were included. The
positive results of tests were revealed in one patient from gastroenterology department with
nonspecific ulcerative colitis that showed high IgG to cardiolipin and betta-2 glycoprotein I
levels, but not IgM. In rheumatology department 3 children with systemic lupus erythematosus
- SLE (10,7% from 28) and 2 patients with juvenile rheumatoid arthritis (9.5% from 21) had
at least one positive marker.
Conclusions: these tests show very rare positive results in children even with clear determine
diagnosis of SLE. It is necessary to use complex approach to establish APS and prevent
thrombus formation.
Abstract 57
Serum markers of antiphospholipid syndrome
detection and their diagnostic significance in the
pediatric practice
Contact / E-Mail:
[email protected], [email protected]
- 87 -
Poster Presentation
Abstract 58
Complement-opsonized HIV overcomes SAMHD1
restriction in DCs
Wilfried POSCH(1), Marion STEGER(1), Ulla KNACKMUSS(1), Felipe DIAZ-GRIFFERO(2),
Cornelia LASS-FLÖRL(1), Arnaud MORIS(3), Oliver T. KEPPLER(4), Doris
WILFLINGSEDER(1)
(1)
(2)
(3)
(4)
Division of Hygiene and Medical Microbiology, Medical University of Innsbruck
Department of Microbiology and Immunology, Albert Einstein College of Medicine
INSERM, U1135, Center for Immunology and Microbial Infections - CIMI-Paris
Institute of Medical Virology, University of Frankfurt
DCs express intrinsic cellular defense mechanisms to specifically inhibit HIV-1 replication. Thus,
DCs are productively infected only at very low levels with HIV-1 and this non-permissiveness
of DCs is suggested to go along with viral evasion. We here give insight into a substantial novel
way of dendritic cell modulation at least during acute HIV-1 infection by triggering integrin
receptor signaling. We found, that complement-opsonization of the virus is able to relieve
SAMHD1 restriction in DCs, thereby initiating strong maturation and co-stimulatory capacity of
the cells and stimulating efficient cellular and humoral antiviral immune responses. This newly
described way of DC modulation by complement might be exploited to find novel therapeutic
targets promoting DC immune functions against HIV.
Acknowledgements
Austrian Science Fund [FWF, P22165 and P24598 to DW, P25389 to WP] and the OeNB
[project: 14875 to WP]
Contact / E-Mail:
[email protected]
- 88 -
Wilfried POSCH(1), Andrea SCHROLL(2), Asier SAEZ-CIRION(3), Gianfranco PANCINO (3),
Teunis GEIJTENBEEK(4), Cornelia LASS-FLÖRL(1), Günter WEISS(2), Doris WILFLINGSEDER(1)
(1) Division of Hygiene and Medical Microbiology, Schöpfstrasse 41, Innsbruck, Austria
(2) Department of Internal Medicine VI, Clinical Immunology and Infectious Diseases, Innsbruck
Medical University, Anichstr. 35, Innsbruck, Austria
(3) Unité de Régulation des Infections Rétrovirales, Institut Pasteur, 25 Rue du Docteur Roux,
75724 Paris, France
(4) Center for Experimental and Molecular Medicine, AMC, University of Amsterdam,
Amsterdam, Netherlands
Poster Presentation
Early on in HIV-1 infection, gut Th17 cells are massively depleted leading eventually to
compromised intestinal barrier function and excessive immune activation. Complement
coating as predominantly found during the acute phase of infection was shown to act as an
endogenous adjuvant for DC-mediated induction of virus-specific CTLs. Here, we show that
DCs loaded with HIV-1 bearing high surface complement levels after incubation in plasma
from HIV-infected individuals, secreted significantly higher concentrations of Th17-polarizing
cytokines compared to DCs exposed to non-opsonized HIV-1. The enhanced Th17-polarizing
capacity of in vitro generated and BDCA1+ DCs was linked to activation of ERK. Additionally,
C3a produced from DCs exposed to complement-opsonized HIV was associated with the
higher Th17 polarization. Our in vitro and ex vivo data, therefore, indicate that complement
opsonization of HIV-1 strengthens DC-mediated anti-viral immune functions by simultaneously
triggering Th17 expansion, intrinsic C3 formation and enhanced CTL responses via DC
activation.
Abstract 59
Triggering CD11b/c on DCs promotes immediate
Th17 polarization during acute HIV-1 infection
Contact / E-Mail:
[email protected]
- 89 -
Poster Presentation
Abstract 60
Evaluation of vaccine responsiveness against tickborne encephalitis (TBE) and hepatitis A in allergic
patients – differences to healthy controls?
Erika GARNER-SPITZER(1), Michael HOFER(1), Reinhard JARISCH(2), Tamar KINACIYAN(3),
Michael KUNDI(4), Ursula WIEDERMANN(1)
(1)
(2)
(3)
(4)
Institute for Specific Prophylaxis and Tropical Medicine, Medical University of Vienna
Allergiezentrum Floridsdorf
Allergieambulanz der Universitätsklinik für Dermatologie, AKH, Medical University of Vienna
Institute for Public Health, Medical University Vienna
Type I allergies have increased drastically and afflict app. 30% of the western population.
Allergic sensitization results in Th2 biased immune responses which eventually trigger allergic
symptoms/diseases. Specific immunotherapy (SIT) is the only causative treatment, leading to
activation of regulatory cells (IL10, TGF-ß) and a shift from Th2 toTh1 response.
In a clinical trial we investigate whether responsiveness to routine vaccines is altered by
allergy: allergic patients, either with SIT or symptomatically treated and healthy controls
receive a booster vaccination against tick-borne encephalitis (TBE). To test primary
responsiveness a subgroup is also vaccinated against hepatitis A.
Immune response is evaluated with respect to specific Ab-titers, cytokine production of restimulated PBMC and quantification of naïve, memory, and regulatory subsets of B- and
T-cells. Additionally, allergic- and SIT-status of participants are correlated with humoral/cellular
immune responses. Preliminary data, namely Ab-titers and B- and T-cell subsets have been
determined for the subgroup receiving both vaccines.
The results of this study will clarify whether allergic sensitization/specific immunotherapy lead
to impaired vaccine responsiveness and demand adaptations of vaccination schedules.
Contact / E-Mail:
[email protected]
- 90 -
Anannya BHATTACHARYA*(1), Ahmed N. HEGAZY*(2,3,4), Nikolaus DEIGENDESCH**(5),
Lindsay KOSACK**(1), Jovana CUPOVIC(6), Richard K. KANDASAMY(1), Andrea
HILDEBRANDT(1), Doron MERKLER(7), Anja A. KÜHL(8), Christopher SCHLIEHE(1), Isabel
PANSE(2,3), Bojan VILAGOS(1), Kseniya KHAMINA(1), Isabelle ARNOLD(4), Lukas FLATZ(6),
Haifeng C. XU(9), Philipp A. LANG(9), Alan ADEREM(10), Giulio SUPERTI-FURGA(1), Jacques
COLINGE(1), Burkhard LUDEWIG(6), Max LÖHNING(2,3),†, Andreas BERGTHALER(1),†
Poster Presentation
(1) CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna,
Lazarettgasse 14 AKH BT25.3, Austria.
(2) Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charité–University
Medicine Berlin, 10117 Berlin, Germany.
(3) German Rheumatism Research Center (DRFZ), a Leibniz Institute, 10117 Berlin, Germany.
(4) Translational Gastroenterology Unit, Experimental Medicine Division Nuffield Dept of Clinical Medicine,
University of Oxford, John Radcliffe Hospital, Oxford, UK.
(5) Max Planck Institute for Infection Biology, Charitéplatz 1, 10117 Berlin, Germany.
(6) Institute of Immunobiology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen,
Switzerland.
(7) Department of Pathology and Immunology, University of Geneva, Centre Médical Universitaire, 1 rue
Michel Servet, 1211 Geneva, Switzerland.
(8) Department of Medicine I for Gastroenterology, Infectious Disease and Rheumatology, Campus
Benjamin Franklin, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.
(9) Department of Gastroenterology, Heinrich-Heine-University, Moorenstr. 5, 40225 Düsseldorf, Germany.
(10) Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 981095219, USA.
*
These authors contributed equally to this work.
**
†
Abstract 61
SOD1 Protects From Type I Interferon-Driven
Oxidative Damage in Viral Hepatitis
Tissue damage caused by viral hepatitis is a major cause of morbidity and mortality worldwide.
It is driven by poorly understood processes involving interrelated immunological and metabolic
events. Using a mouse model of viral hepatitis, we identified virus-induced early transcriptional
changes in the redox pathways including downregulation of superoxide dismutase 1 (Sod1) in
the liver. Sod1-/- mice exhibited increased inflammation and aggravated liver damage upon
viral infection, which was ameliorated by antioxidant treatment. Thus, oxidative stress is a key
mediator of virus-induced liver damage. Type I interferon (IFN-I) led to the downregulation of
Sod1 in wildtype mice and caused oxidative liver damage in Sod1-/- mice in the absence of
infection. Notably, blockade of IFN-I signaling protected against virus-induced liver damage.
These results delineate a novel mechanism of innate immunity-driven immunopathology,
linking IFN-I signaling with antioxidant host defense and infection-associated tissue damage.
Acknowledgements
A.Bh. is supported by a DOC fellowship of the Austrian Academy of Sciences. A.N.H. and
R.K.K. were supported by a European Molecular Biology Organization (EMBO) long-term
fellowship (ALTF 116-2012 and ALTF 314-2012). A.H. was supported by a stipend of the
German Academic Exchange Service (DAAD). C.S. was supported by a fellowship within the
Postdoc-Program of DAAD. G.S.-F. was supported by the ERC advanced grant i-FIVE. M.L.
was supported by the German Federal Ministry of Education and Research (BMBF, T-Sys), the
German Research Foundation (SFB618, TPC3; SFB650, TP28), and the Volkswagen Foundation
(Lichtenberg program). A.B. was supported by the Austrian Academy of Sciences and by standalone grant #23991 of the Austrian Science Foundation (FWF).
Contact / E-Mail:
[email protected]
- 91 -
Poster Presentation
Abstract 62
Comparison of the immunogenicity and
reactogenicity after subcutaneous (s.c.) or intra
muscular (i.m.) vaccination with a tick-borne
encephalitis vaccine
Stefan HOPF(1), Erika GARNER-SPITZER(1), Michael HOFER(1), Ingrid DEMEL(1), Michael
KUNDI(2), Otfried KISTNER(3) and Ursula WIEDERMANN(1)
(1) Institute of Specific Prophylaxis and Tropical Medicine, Center of Pathophysiology,
Infectiology & Immunology, Medical University Vienna, Austria
(2) Institute of Environmental Health, Medical University of Vienna, Austria
(3) Clinical Virology & Scientific Affairs, BioScience, Baxter Innovations GmbH, Vienna, Austria
Studies to determine the optimal vaccination route are being performed during the licensing
studies for all vaccines evaluating immunogenicity and reactogenicity. However in various
situations the vaccine might be applied subcutaneously. For this reason, the following study
was performed to compare the immunogenicity and safety between s.c. and i.m. vaccination.
Neutralizing antibodies, lymphocyte population distribution, cytokine production and the
occurrence of side effects were analyzed and compared for both vaccination routes.
Neutralizing TBE specific antibody titers and cytokine production upon antigen restimulation
of isolated PBMCs did not significantly differ between the different vaccination groups. FACS
analysis revealed only slight differences in naïve and memory lymphocyte populations between
genders and vaccination routes, which however, did not have an obvious influence on vaccine
specific humoral and cellular responses.
Monitoring of side effects after vaccination showed a significant increase in local reactions after
s.c. vaccine application compared to i.m. vaccination. Moreover women showed higher rates of
side effects than men.
The results show that the TBE vaccine can be applied either s.c. and i.m. leading to a
comparable immune response. However, with respect to local side reactions the s.c. route
seems to promote reactogenicity.
Contact / E-Mail:
[email protected]
- 92 -
Mario BIAGGIO(1), Caroline LASSNIG(1,2), Rita ROM(1), Astrid KRMPOTIC(3), Stipan
JONJIĆ(3), Birgit STROBL(1) and Mathias MÜLLER(1,2)
(1) Institute of Animal Breeding and Genetics, University of Veterinary Medicine, Vienna,
Austria
(2) University Center Biomodels Austria, University of Veterinary Medicine, Vienna, Austria
(3) Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Croatia
Poster Presentation
Cytomegalovirus (CMV) infection is a frequent cause of congenital birth defects and can
trigger severe life-threatening disease in immune suppressed individuals. Murine CMV closely
resembles human CMV and is commonly used as model system to study acute and persistent
viral infections. While NK and T cells play a predominant role in eliminating infected cells, the
contribution of myeloid cells to the anti-MCMV defence is largely elusive. Signal transducer
and activator of transcription 1 (STAT1) is a key transcription factor in signalling in response
to all types of interferon and lack of STAT1 results in high susceptibility to bacterial and viral
infections in humans and mice. Our laboratory has generated mice that specifically lack STAT1
in myeloid cells (Stat1ΔLysz), enabling us to study the importance of myeloid antiviral activity
in vivo. Stat1ΔLysz mice showed an increased viral load and increased pathology in spleen and
liver early after infection compared to littermate controls. Intriguingly, Stat1ΔLysz mice did not
show decreased survival but a higher persistence of MCMV in salivary glands. We found similar
activation of splenic and liver NK cells, whereas preliminary experiments show differences
in CD8+ and CD4+ T cell activation. Current efforts are directed towards a more detailed
characterization of anti-MCMV responses in distinct T cell subsets.
Abstract 63
STAT1 in myeloid cells is required to limit
early replication and persistence of murine
cytomegalovirus in vivo
Acknowledgements
This work is funded by the FWF DK W1212 and the SFB F28 to BS and MM.
Contact / E-Mail:
[email protected]
- 93 -
Poster Presentation
Abstract 64
T cell- independent boost of Memory IgE responses
by B cell epitopes
Meena NARAYANAN(1), Margarete FOCKE-TEJKL(2), Rudolf VALENTA(1,2), Birgit LINHART(1)
(1) Div.of Immunopathology, Dept.of Pathophysiology and Allergy Research, Center of
Pathophysiology,Infectiology and Immunology, Medical University of Vienna, Austria
(2)Christian Doppler Laboratory for Allergy Research, Medical University of Vienna, Austria
IgE-mediated allergy is characterized by the induction of allergen-specific Th2 response and
production of allergen-specific IgE antibodies. Although many clinical studies have shown that
IgE levels are boosted by repeated allergen contact, mechanisms underlying secondary IgE
responses are not yet fully understood. Hence, aim was to study the molecular and cellular
requirements for boosting allergen-specific IgE responses.
We developed a mouse model based on hapten-carrier model, where 4 copies of a 31 amino
acid peptide derived from Phl p 1, devoid of T cell epitopes recognized by BALB/c mice, was
fused to a carrier, PreS and used for sensitization. Then,boosting was done with molecules
containing peptide without or with an immunologically irrelevant carrier. For control purposes,
boosting were also done with the same immunogen used for sensitization, carrier alone and
PBS. Peptide-specific IgE responses determined by ELISA and RBL assays showed oligomeric
peptides devoid of T cell epitopes could boost memory IgE responses. T cell responses studied
by proliferation assays using mouse splenocytes failed to proliferate when stimulated with
peptide, which attests the lack of allergen-specific T cell epitopes. Our results suggest B cell
targeting approaches for established allergy.
Acknowledgements
Supported by grant P23350-B11 (FWF), Vienna, Austria.
Contact / E-Mail:
[email protected]
- 94 -
K. Oida (1,2), L. Einhorn (1,3), S. Vrtala (4,5), Y. Resch (4), L. Panakova (6), F. Roth-Walter
(1), J. Fazekas (1,3), H. Matsuda (2), A. Tanaka (7), E. Jensen-Jarolim (1,3)
Poster Presentation
Vienna, Medical University Vienna and University Vienna, Austria
(2) Laboratory of Veterinary Molecular Pathology and Therapeutics, Division of Animal Life
Science, Institute of Agriculture, Tokyo University of Agriculture and Technology, Japan
(3) Comparative Immunology and Oncology, Institute of Pathophysiology and Allergy Research,
Center of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria
of Pathophysiology, Infectiology and Immunology, Medical University Vienna, Austria
(5) Christian Doppler Laboratory for the Development of Allergen Chips, Medical University
Vienna, Austria
(6) Department for Companion Animals and Horses, University of Veterinary Medicine Vienna,
Austria
(7) Laboratory of Comparative Animal Medicine, Division of Animal Life Science, Institute of
Agriculture, Tokyo University of Agriculture and Technology, Japan
Abstract 65
House dust mite extract is a robust source of
enzymes that impair epithelial barrier function
Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disorder. It is accepted
that epithelial barrier dysfunction or disruption must be the initial event before sensitization.
There is on the other hand a strong correlation between house dust mite (HDM) exposure and
AD. HDMs are harmless per se, but are a source of allergens including such with enzymatic
function.
We investigated here the barrier disruption potential of HDM proteases by gel zymography
in vitro using whole body extract from Dermatophagoides pteronyssinus. Regardless of the
presence of Ca and Zn ions, and of a wide range of temperature, HDM extract degraded casein
(as a readout for serine and cysteine protease activity) and gelatin gels (for collagenase
activity). The HDM extract exhibited proteolytic activity at pH 5.0−9.0, thus by far exceeding
the pH range of normal stratum corneum at pH 4.5−5.5.
Exposure to HDM on a daily basis may play a crucial role in the onset of AD by impairing
epithelial integrity via several enzymatic activities and by delivering allergens deep into
the skin. This activity is independent on metal ions, temperature and effective in a wide pH
range. The mechanism thus is robust and allows for penetration into the skin of even healthy
individuals, depending on the dose.
Contact / E-Mail:
Presenting author: [email protected]
Corresponding author: [email protected]
- 95 -
Poster Presentation
Abstract 66
Rise of total IgE levels upon omalizumab treatment
is not due to activation of IgE+ memory B cells
Julia ECKL-DORNA (1), Renate FRÖSCHL (1), Christian LUPINEK (1), Renata KISS (1),
Katharina MARTH (1), Raffaela CAMPANA (1), Katharina BLATT (1), Peter VALENT (1), Regina
M. SELB (1), Andrea MAYER (1), Katharina GANGL (1), Irene STEINER (1), Philippe GEVAERT
(2), Rudolf VALENTA (1), Verena NIEDERBERGER (1)
(1) Medical University of Vienna, Spitalgasse 23, A-1090 Vienna, Austria AND (2) Upper Airway
Research Laboratory (URL), Ghent University Hospital, Sint-Pietersnieuwstraat 25, Ghent,
Belgium
Omalizumab targets free IgE and inhibits its binding to mast cells. Interestingly during
omalizumab therapy an increase in total serum IgE levels has been observed. In this study
we investigated whether the latter is caused by a prolonged half-life of IgE upon complex
formation with omalizumab or by enhanced IgE production of IgE+ memory B cells upon
crosslinking of their B cell receptor with omalizumab.
Total and allergen-specific serum IgE were determined in patients before and after
subcutaneous treatment with omalizumab (n=15) or placebo (n=5).Omalizumab treated
patients showed a 2-6 fold increase of total IgE and a polyclonal rise in specific IgE. To
investigate whether this rise could be due to enhanced IgE production by IgE+ memory B
cells, we intranasally challenged patients (5/group) with omalizumab, placebo or Bet v 1 and
measured total and allergen-specific IgE before and 8 weeks after the challenge. Intranasal
omalizumab did not induce a change in total or allergen-specific serum IgE. A rise of Bet v
1-specific serum IgE was observed in Bet v 1 challenged patients as previously reported.
Furthermore we tested the effect of omalizumab on IgE production by B cells in vitro.
Omalizumab did not increase IL-4 and anti-CD40 induced IgE production in culture.
In summary, we observed no effect of omalizumab on IgE production. Thus the total IgE
increase is likely to be caused by complex formation of omalizumab with IgE in the blood,
thereby prolonging its half-life.
Contact / E-Mail:
[email protected]
- 96 -
Daniela PUCCIARELLI(1), Nina LENGGER(1), Martina TAKÁČOVÁ(2), Heimo BREITENEDER(1),
Silvia PASTOREKOVA(2), Christine HAFNER(1,3)
Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
(2) Institute of Virology, Department of Molecular Medicine, Slovak Academy of Sciences,
Bratislava, Slovakia
(3) Karl Landsteiner Institute for Dermatological Research, St.Poelten, Austria
Poster Presentation
Melanoma is associated with an activating mutation in the gene encoding for BRAF.
Vemurafenib is an inhibitor of the BRAF V600 mutation which arrests the cell-cycle and induces
apoptosis in melanoma cells. One of the main factors which could affect the response to the
drug is an inadequate supply of oxygen. We investigated the effects of hypoxia on melanoma
cell cultures treated with vemurafenib. Three BRAF V600 mutant melanoma cell lines (M14,
518A2 and A375) were cultivated in hypoxia (2% pO2). Antiproliferative effects were
evaluated in a real-time setting in the impedance-based x-CELLigence® system. In hypoxia,
vemurafenib-treated M14 and 518A2 cells reduced cell growth (-40% and -38%) compared
to normoxic, vemurafenib-treated cells. Surprisingly, hypoxic vemurafenib-treated A375 cells
showed an enhanced cell proliferation rate (+34%) when compared to normoxic, vemurafenibtreated A375 cells. WB analyses of HIF1alpha and proteins involved in PI3K, JAK-STAT and
MAPK pathways were performed. The expression of HIF1alpha was reduced in vemurafenibtreated M14 and 518A2 cells but not in A375 cells and was also detected in xenografted tumor
samples. The results suggest that hypoxia alters the gene-expression pattern of proliferative
melanoma cells in a cell-type specific manner.
Abstract 67
Hypoxia contributes to melanoma phenotype change
by affecting the response to vemurafenib
Acknowledgements
This project is a part of the EU Marie Curie Initial Training Networks (ITN) Biomedical
engineering for cancer and brain disease diagnosis and therapy development: EngCaBra.
Project no. PITN-GA-2010-264417.
Contact / E-Mail:
[email protected]
- 97 -
Poster Presentation
Abstract 68
Novel approach for combined treatment of birch
pollen and associated food allergies
Heidi HOFER(1), Claudia ASAM(1), Michael HAUSER(1), Peter BRIZA(1), Christof EBNER(2),
Fatima FERREIRA(1), Michael WALLNER(1)
(1) University of Salzburg, Department of Molecular Biology, Salzburg, Austria
(2) Allergieambulatorium Reumannplatz, Vienna, Austria
Background: Birch pollen allergy is often accompanied by the oral allergy syndrome (OAS)
towards fruits nuts and vegetables. It is triggered due to similar structure of the food allergens
and the major birch pollen allergen Bet v 1. At present, only allergen immunotherapy (AIT) can
meet the disease.
Methods: To address birch pollen and associated food allergies towards apple and hazelnut,
we designed a hybrid protein (MBC4) comprising of T cell epitope containing stretches of all
three allergens. In order to diminish IgE binding capacity a specific mutation was introduced.
Humoral and cellular immune responses were screened to examine immunogenic and
allergenic behavior of the hybrid molecule.
Results: The MBC4 molecule showed an altered folding verified by circular dichroism, and also
significantly reduced IgE binding in comparison to parental allergens. In an in vivo mouse
model we examined its immune regulatory behavior.
Conclusion: Reduced IgE binding of the MBC4 molecule reveals it as a hypoallergen, but even
though the folding of the protein is disrupted, it remains immunogenic. Therefore, we think,
that the novel hybrid protein seems to be a promising vaccine candidate for treatment of birch
pollen and associated food allergies.
Key words: birch pollen allergy, oral allergy syndrome (OAS)
Contact / E-Mail:
[email protected]
- 98 -
Implications for antigen uptake and dendritic cell
polarization
Christoph HILLEBRAND, Almedina ISAKOVIC, Josef THALHAMER, Richard WEISS
University of Salzburg, Department of Molecular Biology, Division of Allergy and Immunology
Poster Presentation
In this study we investigated the humoral immune response in non-allergic donors from
different environments and the impact of allergen specific IgG on antigen uptake and
immune polarization. We found that donors living in a farming vs. urban environment differed
concerning the percentages of IgG responders. Townspeople showed a higher rate of IgG
antibody production than farmers. These differences in the seroconversion indicate that the
environment and the amount of antigen exposure might have an influence on the immune
response. Furthermore we showed that antigen uptake by CD1c+ myeloid dendritic cells in
the presence of autologous plasma is highly dependent on IgG. We therefore established the
methodology to measure gene expression of Fc receptors and immune polarizing genes in DCs
that have taken up the antigen and their capacity to polarize T cell responses. Our preliminary
results indicate that CD1c+ that have taken up allergen/IgG immune complexes highly differ
in their gene expression and polarizing potential between individual donors. Taken together,
we have established the methodology to investigate the impact of living conditions on IgG
mediated DC polarization and the maintenance of T cell responses in non-allergic individuals.
Abstract 69
Allergen specific antibody responses in non-atopic
humans.
Contact / E-Mail:
[email protected]
- 99 -
Poster Presentation
Abstract 70
Monitoring the induction of blocking antibodies
during birch pollen AIT
Sara HUBER(1), Heidi Hofer(1), Roland LANG(2), Thomas HAWRANEK(2), Michèle RAUBER(3)
(4), Fatima FERREIRA(1), Michael WALLNER(1)
(2) Department of Dermatology, Paracelsus Medical University Salzburg, Salzburg, Austria
Austria
(4) Clinical and Experimental Allergology, Department of Dermatology and Allergology, Philipps
University Marburg, Germany
Background: Bet v 1 represents the major allergen in birch pollen showing a sensitization rate
of 95%. At present, allergen immunotherapy (AIT) represents the only curative approach to
meet the disease. The induction of so called blocking antibodies denotes a hallmark of the
treatment; however, treatment-induced allergen-specific IgG levels do not necessarily correlate
with clinical success.
Methods: Five birch pollen-allergic patients were treated with conventional birch pollen AIT
and sera were taken before treatment, after reaching the maintenance dose, and after 1 year
follow-up. The humoral immune response during therapy was monitored by facilitated antigen
binding (FAB) assays and ELISA.
Results: All patients showed an improvement of nasal provocation scores during AIT. Specific
IgE levels were initially boosted; but declined during treatment. This was accompanied by
the induction of allergen-specific IgG. All donors developed blocking antibodies during AIT as
demonstrated by FAB assays.
Conclusion: We did not find a correlation of either IgG or IgE titers with clinical data collected
throughout the study. In FAB assays we could measure the capacity of AIT-induced IgG
to block IgE/allergen complex formation, which correlated well with clinical success of the
treatment.
Key Words: AIT, blocking antibodies
Contact / E-Mail:
[email protected]
- 100 -
Maria Alejandra PARIGIANI(1), Yoan MACHADOf(1), Sabrina WILDNER(1), Peter BRIZA(1),
Lorenz AGLAS(1), Martin WOLF(1), Fátima FERREIRA (1), Michael WALLNER(1)
Poster Presentation
Background: Codons are not used with equal frequencies across species. Synonymous
codons were demonstrated to be critical in shaping cellular processes as they affect protein
expression, structure and/or function. Disparities in codon usage between different organisms
are a common reason for failure in heterologous gene expression often leading to misfolded or
insoluble products. Therefore, the DNA sequence of the major birch pollen allergen Bet v 1 was
modified to resemble the codon usage of E. coli.
Methods: Several batches of Bet v 1 and its codon harmonized homologue Bet v 1 Harm were
produced in E. coli and purified to homogeneity. All batches were extensively characterized
with an array of physico-chemical methods to detect possible effects of codon harmonization
on protein folding.
Results: Harmonization of the Bet v 1 resulted in a significantly increased protein yield
compared to wild-type Bet v 1. However, no differences in the primary or secondary structure
of the protein were observed.
Conclusion: Codon harmonization of the allergen Bet v 1 was shown to increase the
heterologous expression of soluble protein whereas no influence on the allergen-fold was
observed. Thus, the method may facilitate industrial scale production of allergenic proteins.
Abstract 71
Codon harmonization enhances heterologous
expression of Bet v 1 in E. coli
Contact / E-Mail:
[email protected]
- 101 -
Poster Presentation
Abstract 72
Role of allergen-based component-divided
diagnostics in choice of allergy therapy approach for
children with pollinosis
M.A SNOVSKAYA., L.S. NAMAZOVA-BARANOVA, O.V. KOZEVNIKOVA, A.K. GEVORKYAN
Federal State Budgetary Scientific Institution “Scientific Centre of Children Health”
RTSS were count and sIgE levels to birch, alder, hazelnut, oak pollen allergens, rBetv1,
rBetv2, rBetv4, rBetv6 were estimated with ImmunoCAP in 62 children (age 5-10 years) with
pollinosis. Then 32 patients got two courses of sublingual ASIT with birch pollen (I group), 30
children had only symptomatic treatment (II group).
Results: All patients had high sIgE levels to pollen allergens and rBetv1 and RTSS >11. sIgE
to minor allergens were in 7 children (Ib group), other patients had no such antibodies (Ia
group).
After the first ASIT 12 children (Ia) had symptoms reduction and 11 from these had decrease
of sIgE to all pollen allergens. No positive results were observed in Ib group. In II group 4
patients had symptoms and sIgE levels reduction.
After the second ASIT 21 patients (Ia) had symptoms reducing (RTSS < 9,3). 19 patients
also showed sIgE levels decreasing. Group Ib had no significant change. II group patients had
clinical improvement in 5 cases.
So effectiveness of ASIT was 34.7% and 67.3% for first and second course respectively.
Conclusion: ASIT efficacy is depend on course therapy numbers. Two course of the therapy
lead to clinical improvement in more than 65% patients. Application of diagnostic approach
with minor allergens provides the accuracy of ASIT prescription.
Acknowledgements
The work performed within the agreement № 14.607.21.0017 with Ministry of Education and
Science of Russia (unique identifier RFMEFI60714X0017)
Contact / E-Mail:
[email protected]
- 102 -
Sophie KITZMUELLER(1,2), Douglas PINHEIRO(1), Thomas KOCHER(2), Johann BAUER(2), Iris
GRATZ(1,2,3)
(3) Department of Dermatology, University of California San Francisco, San Francisco,
CA, USA
Poster Presentation
Epidermolysis bullosa (EB) is a blistering disease, caused by mutations of anchoring proteins in
the skin. Replacing defective genes by ex vivo gene therapy and subsequent transplantation of
skin grafts is among the most promising approaches for treating EB. However, graft acceptance
may be complicated by the risk of an immune response against the neo-antigen expressed
in the graft. Therefore one critical aspect for the success of this treatment is the induction
and maintenance of tolerance towards the neo-antigen. In a polyclonal system mimicking the
transplantation of a corrected skin graft in a patient with a null mutation we could show that
the immune response against an epidermal neo-antigen leads to rejection of the grafted tissue.
To analyse the underlying mechanisms we also established a monoclonal grafting model. In
this model we transfer antigen (Ovalbumin) restricted CD4+ T-cells (DO11.10 TCR-tg) into
mice which receive grafts expressing Ovalbumin as a neo-antigen and follow the antigenspecific responses in vivo. Analyzing skin grafts showed an impact of CD4+ T-cells to graft
rejection. Our hypothesis that antigen-specific Treg cells can attenuate this process will serve
as a basis for future immunomodulatory approaches to prevent the loss of transplanted skin
grafts.
Abstract 73
Immunity towards neo-antigen in skin grafts: Mouse
models for skin gene-therapy
Acknowledgements
We thank Debra Austria (EB Immunologie) and the University of Salzburg for funding this
project.
Contact / E-Mail:
[email protected]
- 103 -
Poster Presentation
Abstract 74
The immune response to laminin 5 in skin gene
therapy in epidermolysis bullosa
Ana I. SANCHO(1,2), Maria M. KLICZNIK(1), Johann W. BAUER(2), Iris K. GRATZ(1,2,3)
(2) Division of Experimental Dermatology and EB House Austria, Department of Dermatology,
(3) Department of Dermatology, University of California San Francisco-School of Medicine, San
Francisco, CA, USA
Background: Junctional epidermolysis bullosa (JEB), a blistering skin disease, can be caused
by mutations in the gene coding for the skin protein laminin 5 (LAM5). No cure is available but
reports suggest ex vivo genetically corrected protein transfer as a therapeutic option. As the
newly introduced gene could induce adverse immune reactivity, especially in protein-deficient
patients, we assess immune responses to LAM5 after ex vivo gene therapy of JEB.
Methods: Proliferation of LAM5-stimulated PBMCs, isolated from a JEB patient, was assessed
before and after grafting. Moreover, LAM5-specific cytokine and antibody levels were
determined by either ELISA or flow cytometry.
Results: The results showed no significant LAM5-specific cell proliferation before or after
grafting. IL6 and IFN-γ were detected in patient’s serum consistent with the presence of
wounds and infections. IL4, IL5 and IL17 were not present. No antigen-specific cytokines and
no antibody titers were observed. We also established a method to follow immune responses in
skin.
Conclusions: These results seem to indicate lack of antigen-specific immune responses after
restoring LAM5 expression and protein functionality, suggesting ex vivo gene therapy of JEB as
a safe therapeutic approach in patients that lack pre-existing immune reactivity.
Acknowledgements
This work was supported by DEBRA Austria (“EB Immunologie”) and the University of Salzburg.
Contact / E-Mail:
[email protected]
- 104 -
Susanne C. DIESNER(1,2), Cornelia SCHULTZ(1), Xue-Yan WANG(3), Katharina BEITL(1),
Franziska ROTH-WALTER(1,4), Denise HEIDEN(1), Anna ONDRACEK(1), Josef SINGER(1), Judit
FAZEKAS(1), Caroline STREMNITZER(1), Thomas EIWEGGER(2), Zsolt SZÉPFALUSI(2), Isabella
PALI-SCHÖLL(1,4), Erika JENSEN-JAROLIM(1,4), Franz GABOR(3) and Eva UNTERSMAYR(1)
Allergen-loaded PLGA-microparticles (MPs) coated with Neuraminidase (NA) from Vibrio cholera
were shown to increase the intestinal uptake via M-cells. Here we aimed to test the safety and
therapeutic efficiency of orally applied NA-coated MPs in naïve and food allergic mice.
To evaluate the safety of six oral administration cycles of ovalbumin (OVA)-loaded MPs,
allergic mice received uncoated or NA-coated MPs or were left untreated. While previously
naïve animals developed significantly elevated OVA-specific serum IgA levels but no cytokine
changes, we found significantly elevated IL-10 and IFN-gamma levels in allergic mice. To
reveal the therapeutic potential of MPs, mice were sensitized with OVA via the oral route and
received six oral immunotherapy cycles using OVA-loaded, uncoated or NA-coated MPs. As
controls, mice were treated with OVA ig, were left untreated, or naïve. Treatment with NAcoated MPs induced an earlier recovery from anaphylaxis indicated by measurement of core
body temperature. Significantly elevated levels of total intestinal IgA and IL-10 production of
stimulated splenocytes were found in mice treated with NA-MPs compared to controls.
Oral immunotherapy with NA-coated, allergen-loaded MPs represents a safe and efficient food
allergy treatment in mice.
Poster Presentation
(2) Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna,
Austria
(3) Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna,
Vienna, Austria
Vienna, Medical University Vienna and University Vienna, Vienna, Austria
Abstract 75
Neuraminidase-coated, allergen-loaded
microparticles are a safe and efficient novel food
allergy treatment option
Acknowledgements
Supported by the Austrian science fund project P21884. EJJ is supported by the Austrian
science fund project SFB F4606-B19, CST and JF by W1205-B09 (CCHD).
Contact / E-Mail:
[email protected]
- 105 -
Poster Presentation
Abstract 76
Development of a humanized mouse model to
study the immune response to skin gene therapy in
epidermolysis bullosa (EB)
Maria M KLICZNIK(1), Eva MURAUER(2), Iris K GRATZ(1,2,3)
(2) Division of Experimental Dermatology and EB House Austria, Department of Dermatology,
(3) Department of Dermatology, University of California San Francisco-School of Medicine, San
Francisco, CA, USA
The skin blistering disease, dystrophic epidermolysis bullosa (DEB), is caused by mutations in
the gene coding for the skin protein Type VII collagen (C7). All therapeutic approaches aim at
introducing the correct skin protein to EB patients. Most patients are deficient in C7 and will
therefore recognize the therapeutic full-length protein as a neo-antigen. The immune reaction
against the neo-antigen will lead to skin inflammation and clearance of C7 protein, which will
diminish or destroy the success of any treatment approach.
Methods: We are developing a humanized EB mouse model to study and manipulate human
immune responses. In this model, we graft human skin and autologous PBMCs to NOD-scid
IL2rγnull (NSG) mice. The reaction of human T cells to skin antigen will then be followed in
vivo in the recipient mice.
Results: Efficiency of the engraftment was analyzed by subtyping immune cells using lineage
cell markers for T, B and myeloid cells. Additionally, we analyzed cytokine production of CD4+
and CD8+ T cells. The results showed that CD4+ and CD8+ T cells could stably engraft,
although CD8+ cell engraftment was favored compared to CD4+ cells. T cells produced high
levels of IFN-γ, which was consistent with the onset of graft versus host disease. While most
myeloid cell types engrafted with good efficiency, no stable B cell population was established.
Conclusions: Using this model we can follow the engraftment of hPBMCs and measure
inflammatory responses mounted against skin antigens.
Contact / E-Mail:
[email protected]
- 106 -
Berislav BOSNJAK*(1), Michela RIBA*(2), Jose Manuel GARCIA-MANTEIGA*(2), Michelle M.
EPSTEIN*(1), Elia STUPKA*(2)
*contributed equally to this work
(1) Medical University of Vienna, Department of Dermatology, DIAID, Experimental Allergy,
Währinger Gürtel 18-20, 1090 Vienna, Austria
(2) Center for Translational Genomics and Bioinformatics, San Raffaele Scientific Institute, Via
Olgettina 58, 20132 Milano, Italy
Poster Presentation
Individual microarray analyses in experimental allergic asthma have identified a large number
of potential regulators and pathways. Relevant genes and pathways underlying disease
pathogenesis may emerge from the integration of these datasets. We selected 6 publically
available datasets for meta-analysis on the basis of the microarray platform and in vivo
experimental protocol. Our strategy was to combine a top down pathway-centered and a
bottom up gene-centered analyses. The first approach consisted of selecting asthma-specific
pathways from a combination of ‘enriched biological terms’ in each individual study. In second
approach, we combined differentially expressed genes from individual datasets to create a
gene list. From 22,690 genes and total of 131 samples, we obtained a core-network of 903
interconnected genes unraveling known (STAT1, RELA) and previously unknown hubs (PPARA,
HCLS1), as well as disease-related pathways, such as T-cell and B-cell mediated immunity,
phagocytosis and circadian rhythm. To validate the analysis, we confirmed the expression
changes of 42 genes in lungs from mice with allergic asthma. The power of this strategy is
the possibility of uncovering key molecules underlying disease pathogenesis utilizing datasets
derived from disparate experiments.
Abstract 77
Novel meta-analysis of gene expression in mouse
allergic asthma
Contact / E-Mail:
[email protected]
- 107 -
Poster Presentation
Abstract 78
5- and 10-year post-relapse survival of pediatric and
young adult sarcoma patients after a dendritic cellbased cancer immunotherapy.
Friedrich ERHART(1), Alexander M. DOHNAL(1), Thomas FELZMANN(2), Philipp FUNOVICS(3),
Leo KAGER(4,5), Volker WITT(4,5), Susanna LANG(6), Carmen VISUS(2)
(1) CCRI, St. Anna Kinderkrebsforschung, Vienna, Austria
(2) Activartis Biotech GmbH, Vienna, Austria
(3) Department of Orthopaedic Surgery of the Medical University of Vienna, Austria
(4) Department of Pediatric and Adolescent Medicine of the Medical University of Vienna,
Austria
(5) St. Anna Children’ Hospital, Vienna, Austria
(6) Department of Pathology of the Medical University of Vienna
Cancer immunotherapy (CIT) based on dendritic cells (DC) is gradually developing into
a more mature therapy option. Our approach involves the microbial danger molecule
lipopolysaccharide in connection with interferon-gamma.
In the years 2000-2008 we recruited 29 children, adolescents and adults suffering from
sarcomas (48% osteosarcoma, 52% other) that had recurrent and/or metastatic disease and
were thus eligible for an experimental therapy (phase I clinical trial). At the time of DC-CIT,
62% were in 2nd or higher complete surgical remission (CR) and 34% in progress; 3% had
stable disease. After DC-CIT, 41% received further multimodal treatment.
In summer 2014 we tracked the outcome of all 29 participants. We registered an overall
5-year survival rate of 31% and 10-year rate of 22% after advent of experimental treatment.
For osteosarcoma alone, we observed respective rates of 36% and 17%. The rate of 5-year
survivors with later additional multimodal therapy is 67%. For any efficacy evaluation, further
clinical studies with a randomized, controlled design will be necessary.
To explore factors associated with long-term survival, we investigated 9 vaccine variables and
74 host immune system variables. A significant association with survival was registered for
helper T cell markers.
Acknowledgements
We would like to thank Gerda Ricken, René Reitermaier, Simone Klingenbrunner and Katrin
Fischhuber for excellent technical assistance.
Contact / E-Mail:
[email protected]
- 108 -
Can225IgG, a new canine anti-EGFR antibody
Although cancer is among the most common causes of death in aged dogs, no passive
immunotherapy has been established yet.
The human and canine Epidermal Growth Factor Receptors (EGFR) show striking homology
as well as similar biological functions. Thus, we generated a canine anti-EGFR antibody
(Can225IgG) in order to introduce passive immunotherapy also for veterinary patients.
The antibody was produced in CHO DUKX-B11 cells and purified via Protein G affinity
chromatography. CD-spectroscopy, immunoassays and cell proliferation assays provided
information about assembly, folding, specificity, inhibitory functions and effector-cell mediated
tumor-cell killing.
We obtained around 120 mg of purified, correctly folded and assembled antibody. Furthermore,
we could demonstrate that signal depletion by Can225IgG was sufficient to reduce proliferation
and viability of tumor cells. Moreover, co-incubation of canine breast cancer cells with canine
monocytes and Can225IgG led to significantly increased phagocytosis of tumor cells.
In conclusion we report the first recombinant canine anti-EGFR antibody with the perspective
of a clinical trial in dogs. In addition, we propose the use of better-suited model organisms for
therapeutic drug studies, speeding up clinical trials for the benefit of both human and canine
patients.
Poster Presentation
(1) Comparative Immunology and Oncology, Institute of Pathophysiology and Allergy Research,
Vienna, Medical University Vienna and University Vienna
(3) Department of Immunology, Capital Medical University, Beijing, P. R. China
(4) Department of Biotechnology, VIBT – BOKU – University of Natural Resources and Life
Sciences, Vienna
(5) Department for Companion Animals and Horses, Clinic for Internal Medicine Small Animals,
University of Veterinary Medicine Vienna, Austria
(6) Immunological Engineering, Department of Engineering, Aarhus University, Denmark
Abstract 79
Judit FAZEKAS(1,2), Josef SINGER(1,2), Wei WANG(3), Marlene WEICHSELBAUMER(1),
Alexander MADER(4), Miroslawa MATZ(1), Willibald STEINFELLNER(4), Yuri SOBANOV(1),
Diana MECHTCHERIAKOVA(1), Michael WILLMANN(5), Edzard SPILLNER(6), Renate
KUNERT(4), Erika JENSEN-JAROLIM(2,1).
Acknowledgements
Supported by grants P 23398_B11 and DK W1205-B09 (CCHD) of the Austrian Science Fund,
by Biomed Int R+D, Vienna, and by RotePfote - Cancer Research for pets. M. Weichselbaumer
was a recipient of a scholarship of the University of Veterinary Medicine Vienna.
Contact / E-Mail:
[email protected]
- 109 -
Poster Presentation
Abstract 80
Neonatal colonization with recombinant lactic acid
bacteria for prevention of poly-sensitization
Priya SARATE(1), Stefan HEINL(2), Hana KOZÁKOVA(3), Reingard GRABHERR(2), Irma
SCHABUSSOVA(1), Ursula WIEDERMANN(1)
(1) Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology,
Immunology and Infectiology, Medical University of Vienna, Vienna, Austria
(2) (c/o CD Laboratory for Genetically Engineered Lactic Acid Bacteria Department of
Biotechnology University of Natural Resources and Life Sciences VIBT, Vienna, Austria
(3) Laboratory of Immunology and Gnotobiology, Institute of Microbiology of Academy of
Sciences of Czech republic,V.V.I., Novy Hradek, Czech Republic
It is well recognized that allergic individuals are at risk to develop multiple allergies and such
poly-sensitized individuals are difficult to treat by conventional therapeutic measures. We
have recently established mouse models of poly-sensitization and demonstrated that allergic
poly-sensitization can be suppressed by mucosal treatment with novel allergen chimers in
adult mice. With respect to neonatal interventions we previously showed that colonization
with recombinant probiotic strains expressing the allergen Bet v 1 successfully prevents
allergic responses. In order to investigate whether the concept of neonatal colonization with
recombinant probiotic bacteria could be used for prevention of allergic multi-sensitivities, we
now have constructed a recombinant Lactobacillus plantarum, constitutively expressing a birch
(Bet v 1) and grass pollen chimer (Phl p 1 and Phl p 5). Next, neonatal colonization will be
performed in order to study the effects and interactions of this recombinant lactobacillus strain
with the host immune system.
Acknowledgements
FWF funding (MCCA program)
Contact / E-Mail:
[email protected]
- 110 -
Manuela ZLAMY(1), Reinhold WÜRZNER(2), Walther PARSON(3), Heidemarie HOLZMANN(4),
Verena JELLER(1), Martina PRELOG(5)
(1)
(2)
(3)
(4)
(5)
Department of PediatricsI, Medical University Innsbruck, Austria
Division of Hygiene and Microbiology, Medical University Innsbruck, Austria
Institute of Legal Medicine, Medical University Innsbruck, Innsbruck, Austria
Clinical Institute of Virology, Medical University of Vienna, Austria
University Children’s Hospital, University of Würzburg, Germany
Poster Presentation
The aging of the immune system (immunosenescence) starts soon after birth with thymus
involution and continues throughout life. T cell immunosenescence is characterized by a
decreased number of naïve T cells, a compensatory autoproliferation of peripheral memory
T cells, an oligoclonal expansion of T cell receptor (TCR) distribution, and an expansion of
perpetuated CD8+ T cells due to chronic viral infections (e.g. CMV). Consequently a low
antibody response to vaccinations and neo-antigens, increased infection rates with associated
morbidity and mortality rates as well as an increased incidence of autoimmune disorders is
described. Former studies assumed that thymectomy in early childhood leads to a premature
immunosenescence, mimicking changes of the aged immune system.
Our study was aimed to investigate whether thymectomy in early childhood may serve
as a model for premature immunosenescence. Therefore changes in the peripheral T cell
subpopulations were measured in thymectomized patients and age-matched controls. Naïve
and memory T cells, intestinal derived naïve T cells (CD103+), IL-7 receptor (CD127)expressing T cells and TCR diversity were analyzed. The influence of serum IL-7 concentrations
and latent CMV infection on specific T cell subpopulations was measured. To determine the
influence of thymectomy on the immune response to neo antigens (tick-borne-encephalitisvirus vaccination and mumps-measles-rubella-vaccination) a clinical study was conducted.
Our study revealed lower percentages of naïve T cells, especially within the CD8+ T cell
pool. We found higher proportions of intestinal derived T cells in thymectomized patients
compared to controls and a peripheral proliferation of pre-existing memory T cells. IL-7 values
in thymectomized patients were slightly higher compared to controls. CMV seropositivity
predicted a more monoclonal TCR distribution in thymectomized patients. Thymectomized
children showed a delayed immune response to neo-antigens but a normal immune response
to revaccination with a live-attenuated vaccine.
Our study demonstrated alterations in the T cell immune system reminiscent of the
immunological changes found in elderly. Thymectomized children represent a unique group
to study the long-term consequences of suboptimal or lacking thymus output. It remains
to be evaluated, if vaccine-specific IgG antibody concentrations of thymectomized children
vanish earlier in later life than in controls, and if immunosenescence parameters accelerate
with advancing age making thymectomized patients prone for inflammatory or degenerative
diseases of the elderly.
Abstract 81
Immune alterations after thymectomy in early
childhood
Contact / E-Mail:
[email protected]
- 111 -
Poster Presentation
Abstract 82
Towards a non-allergenic peptide mix containing the
T cell epitopes of relevant house dust mite allergens
Huey-Jy HUANG(1), Mirela CURIN(1), Srinita BANERJEE(1), Kuan-Wei CHEN(1), Tetiana
GARMATIUK(1), Yvonne RESCH(1), Raffaela CAMPANA(1), Margarete FOCKE-TEJKL(1), Rudolf
VALENTA(1), Susanne VRTALA(1,3)
for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
(2) Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical
University of Vienna, Vienna, Austria
(3) 3Christian Doppler Laboratory for the Development of Allergen Chips, Department of
Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria
Der p 1, Der p 2, Der p 5, Der p 7, Der p 21 and Der p 23 are the most important house
dust mite (HDM) allergens. The aim of this study was to define a mix of non-allergenic T cell
epitope-containing peptide mix of these allergens for tolerance induction. According to the
amino acid sequences of these allergens we were able to synthesize 36 overlapping peptides
covering the complete sequences of the 6 HDM allergens on a peptide synthesizer. The
peptides could be purified in large amounts. They lacked secondary structure but most of them
remained soluble in physiological buffers. Testing of the peptides for IgE reactivity with sera
from HDM allergic patients showecker testing of the peptides for their ability to stimulate T
cells was performed with PBMCs from HDM allergic patients using a CFSE dilution-based assay
showing the presence of relevant HDM T cell epitopes in the peptides.
Our results indicate that it may be possible to identify a hypoallergenic T cell epitopecontaining peptide mix of the clinically relevant HDM allergens for tolerance induction.
Contact / E-Mail:
[email protected]
- 112 -
Ruth BYRNE(1), Karolina VON DALWIGK(1), Günter STEINER1, Johannes HOLINKA2, Reinhard
WINDHAGER2, Josef S. SMOLEN1, Hans KIENER1, Clemens SCHEINECKER(1)
(1) Division of Rheumatology
(2) Department of Orthopedics, Medical University of Vienna, VIENNA, Austria
Poster Presentation
The synovial lining tissue consists of fibroblast-like synoviocytes (FLS) and monocyte-derived
macrophage-like synoviocytes (MLS) within a self-built meshwork of dense extracellular matrix
(ECM) components. FLS are thought to direct ECM synthesis, assembly and degradation.
Whether FLS themselves or the ECM network serve as guiding structures for MLS migration is
incompletely understood.
We studied the dynamics of synovial tissue modeling as well as MLS migratory behavior using
a 3D synovial tissue in vitro model. Human FLS were prepared from synovial tissues obtained
as discarded specimens following joint arthroplasty. CD14+ monocytes (MO) were isolated
from peripheral blood. FLS and MO were labeled with fluorescent membrane dyes and cultured
in spherical extracellular matrix micromasses with an average size of 1.5 mm for up to two
weeks. Second harmonic generation was used for the visualization of collagen fibers (ECM).
Cell migration was monitored in individual micromasses by real-time confocal/multi-photon
microscopy.
The formation of a synovial lining-like layer on the outside of the 3D cell culture takes 2 – 3
days. The first signs of collagen fibers co-localized with FLS clusters and appear as early as day
1. They increase density alongside the establishment of the lining layer.
The majority of MO was found to be in close contact with the FLS network with low tendency
for migration. A minor fraction of MO displayed directed cell movement with an impressive
maximum speed of up to 15 mcm/min. MO migration occurred in intimate contact with FLS
but did not necessarily follow FLS network boundaries, but rather the cell cultures surface.
However, for sitting as well as migrating MO contact with FLS seems to be more important than
contact with ECM.
The 3D synovial tissue culture system allows for monitoring and analyzing the dynamics of
synovial lining modeling. Both, FLS and MO appear to cooperate in the organization of the
synovial lining tissue with subtle migration patterns of MO in relation to the organized synovial
lining architecture. Ongoing experiments address molecular mechanism(s) of MO – FLS
interaction in order to identify potential targets for future therapeutic intervention in arthritis.
Abstract 83
The fibroblast network serves as guiding structure
for directed monocyte migration in 3D synovial
tissue cultures
Contact / E-Mail:
[email protected]
- 113 -
Poster Presentation
Abstract 84
Selective activation of cannabinoid receptor 2 primes
eosinophils for enhanced migratory responsiveness
Robert FREI, Gerald PARZMAIR, Silke SCHRANZ, Akos HEINEMANN, Eva STURM
Inst. of Experimental and Clinical Pharmacology, Medical University of Graz;
Universitätsplatz 4, 8010 Graz, Austria
Accumulation of eosinophils in tissue is a hallmark of allergic inflammation. The
endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil
migration in a CB2 receptor/Gi/o-dependent manner. However, it was claimed recently that
besides CB2 activation, 2-AG metabolites and the 15-lipoxygenase pathway are involved in the
regulation of eosinophil migration induced by 2-AG. Here we explored the direct contribution of
specific CB2 receptor activation to eosinophil effector function. We observed that the selective
CB2 agonist JWH-133 potently enhanced chemoattractant-induced eosinophil shape change,
chemotaxis, CD11b expression and adhesion. Moreover, selective CB2 stimulation evoked
an increase in intracellular Ca2+ and mediated the activation of MAPK-kinase 1/2 and Rhoassociated protein kinase via a pertussis toxin-insensitive G-protein. These data indicate that
direct CB2 receptor activation primes eosinophils for an enhanced migratory responsiveness
towards proinflammatory agents. Given its abundant expression in eosinophils and other
inflammatory cells, antagonism of the CB2 receptor may be of therapeutic relevance in allergic
inflammation and other eosinophilia-associated disorders.
Acknowledgements
We thank Birgit Brodacz and Iris Red for their skilled technical assistance.
Contact / E-Mail:
[email protected]
- 114 -
Barbara PLATZER (1), Kutlu G. ELPEK (2), Viviana CREMASCO (2), Kristi BAKER (3), Cornelia
SCHULTZ (1, 4), Eleonora DEHLINK (1, 5) Kai-Ting C. SHADE (6), Robert M. ANTHONY (6),
Richard S. BLUMBERG (3), Shannon J. TURLEY (2) and Edda FIEBIGER (1)
Epidemiologic studies discovered an inverse association between IgE-mediated allergies
and cancers. Mechanistic details as to how IgE contributes to tumordefense remain poorly
understood. Using a humanized mouse model that mirrors expression of Fc-epsilon-RI,
the high affinity IgE receptor, on dendritic cells (DCs) as seen in humans at steady state
in the absence of inflammation, we demonstrate a novel IgE-mediated cross-presentation
pathway. This cross-presentation pathway is executed by the CD8-negative DC subset in
an IgE-dependent manner and is particularly potent in inducing cytotoxic T cells in response
to low-dose soluble antigen. Interestingly, co-administration of danger signals and IL-12
are dispensable for efficient IgE-mediated cross-presentation. In classical tumor vaccination
experiments with the B6-melanoma model, DCs that are loaded ex vivo with tumor antigen
through IgE/Fc-epsilon-RI prevent tumor growth more potently than DCs loaded without IgE.
In summary, our study delineates a novel cross-presentation pathway for soluble antigens
that relies on the DC-bound IgE pool. Furthermore, our findings point to IgE-mediated crosspresentation as a target pathway to improved DC-based tumor vaccination strategies as
currently developed for cancer therapy in humans.
Poster Presentation
(1) Division of Gastroenterology and Nutrition, Boston Children’s Hospital and Department of
Pediatrics, Harvard Medical School, Boston, MA 02115, USA
(2) Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA
02115, USA
(3) Division of Gastroenterology, Brigham and Women’s Hospital and Department of Medicine,
Harvard Medical School, Boston, MA 02115, USA
Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria
(5) Department of Pediatrics and Adolescent Medicine, Division of Pediatric Pulmology,
Allergology and Endocrinology, Medical University of Vienna, 1090 Vienna, Austria
(6) Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital,
Harvard Medical School, Boston, MA 02129, USA
Abstract 85
Dendritic cells use IgE-mediated antigen crosspresentation to generate cytotoxic T cells in
response to low dose soluble antigen
Acknowledgements
This work was supported by grants from the National Institutes of Health: K01DK093597 (to
B.P.), DK53056 (to R.S.B.), 5R01 DK074500-08, 2P01AI045757-15, R21 CA182598-01 (to
S.J.T.), T32 CA 070083-15 (to V.C.) and AI075037 (to E.F.) and by the Harvard Digestive
Diseases Center Grant P30DK034854.
Contact / E-Mail:
[email protected]
- 115 -
Poster Presentation
Abstract 86
HAX1 deletion impairs BCR-internalization, leading
to delayed apoptosis of mature B cells
Gertrude ACHATZ-STRAUSSBERGER
Department of Molecular Biology, Division of Allergy and Immunology, University of Salzburg
HAX1 was identified in our group as an IgE-tail interacting protein. To determine the impact
on IgE receptor mediated signaling we deleted HAX1 in mice, which caused a severe reduction
in the number of lymphocytes in spleen, with an almost 70% reduction of B220+ cells. To
explain the reduced cellularity of Hax1-/- mice and as HAX1 was thought to play a protective
role in apoptotic processes, we investigated the general viability for bone marrow B progenitor
cells and splenic B cells. The general survival of Hax1-/- bone marrow cells was inconspicuous,
whereas Hax1-/- splenocytes showed elevated survival. By focusing on B220 cells, we showed
decreased apoptosis of IgM stimulated splenic B cells, which by trend was also visible for
B220 bone marrow cells. This, as we suggest, is reasoned by an impaired internalization of
the BCR from Hax1-/- splenic B cells after IgM crosslinking. We strongly suggest an important
role for HAX1 in BCR mediated internalization events, as we showed a tight interaction to the
cytoplasmic domains of IgG1, IgG2a and IgE and identified KVKWI(V)F as the putative binding
motif at the cytoplasmic domains. IgE B cells are considered to be prone for apoptosis. As the
main function of HAX1 was found in the inhibition of apoptosis, we further want to investigate
the impact on the apoptosis prone phenotype of mIgE B cells.
Contact / E-Mail:
[email protected]
- 116 -
Hanane LANAYA(1)*, Anuradha NATARAJAN(1)*, Karin KOMPOSCH(1)*, Liang LI(2), Nicole
AMBERG(1), Stefanie K. WCULEK(1), Martina HAMMER(1), Rainer ZENZ(1), Markus PECKRADOSAVLJEVIC(3), Wolfgang SIEGHART(3), Michael TRAUNER(3), Hongyang WANG(2), Maria
SIBILIA(1)
Hepatocellular carcinoma (HCC) is the sixth most frequent cancer with limited treatment
options and poor prognosis. Tumorigenesis has been linked with macrophage-mediated
chronic inflammation and diverse signaling pathways including the Epidermal Growth Factor
Receptor (EGFR) pathway. The precise role of EGFR in HCC is unknown, and EGFR inhibitors
have shown disappointing results in clinical trials likely due to the lack of biomarkers allowing
patient stratification. Here we discover that EGFR is expressed in liver macrophages in
both human HCC and in a mouse HCC model. Mice lacking EGFR in macrophages show
impaired hepatocarcinogenesis, whereas mice lacking EGFR in hepatocytes unexpectedly
develop more HCC due to increased hepatocyte damage and compensatory proliferation.
The presence of EGFR-positive liver macrophages in HCC patients is associated with poor
survival. Mechanistically, following IL-1 stimulation, EGFR is required in liver macrophages
to transcriptionally induce IL-6, which triggers hepatocyte proliferation and HCC. This study
highlights the complexity of EGFR signaling in HCC and demonstrates a new tumor-promoting
mechanism for EGFR in non-tumor cells, which could lead to more effective precision medicine
strategies.
Poster Presentation
(1) Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center,
Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
(2) National Center for Liver Cancer, International Cooperation Laboratory on Signal
Transduction, Eastern Hepatobiliary Surgery Institute/Hospital, Shanghai, 225 Changhai Road,
Shanghai 200438, China.
(3) Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Division
of Gastroenterology and Hepatology, Medical University of Vienna, Währinger Gürtel 18-20,
1090 Vienna, Austria.
*These authors contributed equally to this work.
Abstract 87
EGFR is required in liver macrophages for IL1-induced IL-6 production and hepatocellular
carcinoma formation
Contact / E-Mail:
[email protected]
- 117 -
Poster Presentation
Abstract 88
Inducible Neo-Antigen Expression in Steady State
Langerhans Cells mediates Immunological Tolerance
Helen STRANDT(1), Veronika HÖPFLINGER(1), Peter HAMMERL(1), Daniel H. KAPLAN (2),
Dagmar WIRTH(3), Josef THALHAMER(1), Angelika STOECKLINGER(1)
(2) Department of Dermatology, Center for Immunology, University of Minnesota, Minneapolis,
USA
(3) Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research,
Braunschweig, Germany
Epidermal Langerhans cells (LC) are highly efficient antigen presenting cells. However, their
function for immune activation or tolerance induction is still not completely solved. To address
the principal biological role of LC in vivo, we have developed transgenic mouse models which
enable de novo antigen expression specifically in LC by Tamoxifen- (TAM) mediated activation
of Cre recombinase. Thus, in these mice neo antigens such as Ovalbumin (OVA), E. coli betaGalactosidase (bGal) or others are presented to the immune system selectively by LC. We
found that antigen expression in resting LC did not induce antibody production however, it
was sufficient for initial activation of OT-1 cells and, moreover, endogenous cytotoxic T cells.
Interestingly, when we looked at later time points, CTL responses were suppressed, even after
antigen challenge with the respective gene gun (GG) vaccine. We found regulatory T cells
(Treg) highly relevant for immunosuppression, since depletion of CD25+ Treg cells, almost
completely restored CTL responses to that of GG-immunized wild type mice. These data
suggest that antigen presentation by resting LC results in T- and B cell tolerance which cannot
be broken by a subsequent inflammatory antigen challenge.
Contact / E-Mail:
[email protected]
- 118 -
Silke SCHROM(1), Sarah AHMADI(1), Barbara DILLINGER(1), Wolfgang HOLTER(1,2),
Alexander DOHNAL(1), Andreas HEITGER(1,2)
(1) CCRI, St. Anna Children’s Cancer Research Institute, Vienna, Austria
(2) Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Austria
Poster Presentation
T cells (TCs), playing a key role in immune reconstitution after hematopoietic stem cell
transplantation (HSCT) and guiding allo-immune reactions against malignant but also normal
host tissues (GvHD) require costimulatory signals for full activation. By interfering with the
CD28 pathway, anergy, i.e. antigen-specific non-responsiveness, is induced.
The tolerizing effect of CD28 blockade via CTLA4-Ig has been described for the CD4+ TC
population. We hypothesize that costimulation blockade (CB) using CTLA4-Ig or an anti-CD28
antibody also affects CD8+ cytotoxic TCs.
Abstract 89
Elucidating the effects of costimulation blockade on
allo-reactive cytotoxic T cells
We performed mixed leukocyte reactions with Balb/c CD3+ TCs stimulated by C57BL/6
dendritic cells. In the presence of CB proliferation of CD8+ TCs was inhibited by ~65%, the
degranulation marker CD107a, intracellular and secreted levels of GzmB and IFN-g were
reduced with no difference using either CTLA4-Ig or anti-CD28. These data suggest that CB
during allostimulation impairs the expansion and/or function of murine CD8+ TCs. We plan
to perform cytotoxic T lymphocyte killing assays using the mouse lymphoma cell line EL4 as
target cells and further elucidate whether CB directly affects CD8+ TCs or via control by CD4+
TCs. Understanding the effects of CB on cytotoxic T cells will be important for further HSCT
research.
Contact / E-Mail:
[email protected]
- 119 -
Poster Presentation
Abstract 90
The role of RGS16 in immune regulation
Bastien A. HUBER(1), Angela HALFMANN(1), Klara SOUKUP(1), Alexander M. DOHNAL(1)
(1) Children’s Cancer Research Institute Vienna – St. Anna Kinderkrebsforschung Wien
Dendritic Cells (DCs) are important in immune regulation to prevent excessive effector T cell
functions after lipopolysaccharide (LPS) encounter. Based on human data from monocytederived DCs we detected a potential target to drive DCs into their regulatory phenotype,
the regulator of G-protein signaling protein 16 (RGS16). Except its mechanical function as
a GTPase turning off G-protein coupled receptor signaling, there is not much known about
RGS16 in DCs.
RGS16 protein is not only present in DCs, we also found it in the supernatant of LPS-stimulated
bone-marrow-derived DCs from mice. Furthermore, DCs silenced for RGS16 expression were
able to induce higher proliferation in CD8+ T-cell populations compared to control DCs.
As we are interested in immune-regulatory mechanisms in the tumor microenvironment we
inoculated B16F10 melanoma into wild-type mice. In tumor-resident DCs mRNA expression
was 2-fold lower than in the respective splenic DCs. However in the tumor cells, RGS16
expression was almost 10-fold higher.
Further investigation will determine the role of RGS16 in immune regulation and its impact in
the tumor microenvironment.
Contact / E-Mail:
[email protected]
- 120 -
David G. MAIRHOFER(1), Vincent FLACHER(2), Christoph H. TRIPP(1), Björn E. CLAUSEN(3),
Suzie CHEN(4), Patrizia STOITZNER(1)
Ectopic expression of the neuronal receptor, metabobotropic glutamate receptor 1 (Grm1),
in melanocytes has been described to be involved in melanoma pathogenesis in human. The
overexpression of Grm1 in melanocytes of the transgenic (tg)(Grm1)EPv mouse strain leads
to spontaneous melanoma development. In this study we characterized the role of skin DC
subsets in cross-priming of CD8+T cells in tumor immunity. Melanoma growth disturbed
the DC network, especially Langerin+dermal DC (dDC) were reduced in skin and lymph
nodes. Functionally this DC subset seemed to be impaired due to lower expression of CD40
and IL-15Rα in tumor mice. In order to highlight the importance of migratory DC in crosspresentation of endogenous tumor-associated gp100 antigen, we crossed tg(Grm1)EPv mice to
LangerinEGFP and Langerin-DTR mice to allow sorting or depletion of various skin DC subsets.
All sorted migratory skin DC subsets were able to cross-present endogenous gp100 antigen
as determined by production of IFN-gamma and Granzyme B by gp100-specific CD8+T cells
from transgenic pmel-1 mice. The depletion of Langerin+dDC and LC in vivo led to a reduction
in proliferation and differentiation of adoptively transferred gp100-specific CD8+T cells. This
effect could be restored when Langerin+dDC repopulated the skin. Our results demonstrate
that skin DC, especially Langerin+dDC, are able to cross-prime CD8+T cell responses against a
tumor-associated antigen, thereby they would be suitable targets for a immunotherapy against
melanoma.
Poster Presentation
(1) Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck,
Austria
(2) Laboratory of Immunopathology and Therapeutic Chemistry, Institute de Biologie
Moléculaire et Cellulaire, Strasbourg, France
(4) Susan Lehman Cullman Laboratory for Cancer Research, Rutgers University, Piscataway,
New Jersey, USA
Abstract 91
Migratory skin dendritic cells are involved in CD8+
T cell responses against the melanoma-associated
antigen gp100
Contact / E-Mail:
[email protected]
- 121 -
Poster Presentation
Abstract 92
T cells from Multiple Myeloma patients exhibit
features of T-cell exhaustion
Claudia ZELLE-RIESER(1), Shanmugapriya THANGAVADIVEL(1), Wolfgang WILLENBACHER (2),
Rainer BIEDERMANN(3), Richard GREIL(1,4) and Karin JÖHRER(1)
(1) Tyrolean Cancer Research Institute, Innsbruck, Austria
(2) Department of Internal Medicine V, Innsbruck Medical University, Innsbruck, Austria
(3) Department of Orthopedic Surgery, Innsbruck University Medical Center, Austria
(4) Laboratory for Immunological and Molecular Cancer Research, IIIrd Medical Department,
Paracelsus Medical University Salzburg, Salzburg, Austria
Immune evasion is a prerequisite for the establishment of cancers and has been delineated
in several entities in detail. Recent studies suggest that immunological alterations involving
the T-cell compartment are responsible for immune deficiencies. However, data in multiple
myeloma are largely missing. Here, we investigated the phenotype and function of bone
marrow and peripheral T cells of myeloma patients and healthy, age-matched donors. We
found an upregulation of T cells expressing the molecules CTLA-4 (CD152), CD57 (human
natural killer-1), 2B4 (natural killer cell receptor 2B4, CD244) and PD1 (programmed
death receptor-1, CD279), which were previously associated with T-cell exhaustion and
T-cell senescence. Functional studies confirmed decreased proliferative capacity of bone
marrow CD8+ T-cells of multiple myeloma patients and downregulation of Tbet after T-cell
activation, confirming the exhausted status of the CD8+ T-cells. Our results suggest that
restoring the functional activity of bone marrow T-cells could enhance the efficacy of current
immunotherapeutic strategies in multiple myeloma patients.
Acknowledgements
This project was supported by a grant of the Austrian Cancer Society/Tirol and the EU-grant
OPTATIO (FP2007-2013, no. 278570)
Contact / E-Mail:
[email protected]
- 122 -
Christoph H. TRIPP(1), Daniela ORTNER(1), Sandrine DUBRAC(1), David E. SCHLÖGL(1),
Kerstin KOMENDA(1), Björn E. CLAUSEN(2) and Patrizia STOITZNER(1)
(1) Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck,
Austria
Poster Presentation
The exposure to chemicals can cause carcinogenesis in the skin leading to the development
of squamous cell carcinoma or basal cell carcinoma. Due to their location, skin dendritic cells
(DC) are the first antigen presenting cells encountering transformed cells. In this project we
wanted to understand the innate mechanisms occurring in chemical carcinogenesis in the
skin. Langerin+ DC/Langerhans cells (LC) proved to be important for early events during
carcinogenesis, because tumor formation was accelerated after application of the carcinogen
7,12-dimethylbenz(a)anthracene (DMBA) on murine skin lacking these two cell types. In
particular, we detected more gamma-H2AX-expressing keratinocytes, indicative of DNA
damage in DMBA-treated skin devoid of Langerin+ DC/LC. The clearance of damaged and
transformed skin cells is mediated by innate cells, such as NK cells. Application of DMBA led
to an accumulation of NK cells in the skin and this process was dependent on the presence of
Langerin+ DC/LC. Moreover, in vivo depletion of NK cells accelerated tumor development in
a similar way as in the absence of Langerin+ DC/LC. Our findings demonstrate an important
link between skin DC and innate effector cells in the clearance of transformed cells preceding
carcinogenesis.
Abstract 93
The role of Langerin-positive skin dendritic cells in
chemical skin carcinogenesis
key words: weed pollen allergens
Contact / E-Mail:
[email protected]
- 123 -
Poster Presentation
Abstract 94
Lowering T cell activation strength in vivo polarizes T
cell differentiation towards a regulatory phenotype
Douglas F. PINHEIRO(1), Sophie SKITZMUELLER(1,3), Maria Magdalena KLICZNIK(1,3),
Gertrude ACHATZ(1), Abul K.ABBAS(2), Iris GRATZ(1,3,4).
(2) Department of Pathology, University of California San Francisco, San Francisco, CA 94143,
USA
(4) Department of Dermatology, University of California San Francisco, San Francisco, CA
94143, USA
Immune homeostasis is governed by a fine balance of pathogenic effector T cells (Teff)
and suppressive regulatory T cells (Treg). Here we aim to define the impact of tissueantigen expression levels on T cell activation strength and its downstream effects on T cell
differentiation. We use two Tetracycline(Tet)-inducible models for expression of ovalbumin
(Ova) in skin. Keratin 5 promoter (K5) is expressed in the basal cell layer and involucrin (INV)
in the upper layers of the epidermis. In these models we can follow adoptively transferred
naïve Ova specific T CD4+ cells (DO11.10) in vivo. We find that K5-Ova-epxression leads to
differentiation of both, Teff and Treg cells, while INV completely blocks Treg differentiation.
Consequently, K5 results in self-resolving skin inflammation while INV leads to fatal disease.
The latter can be reversed by in vivo Treg generation prior to Ova-induction. We found that
INV leads to higher expression levels, which we can titrate by dilution of Tet. This reduces
proliferation and production of effector cytokines and restores Treg cell differentiation. Taken
together, this suggests that antigen load and initial TCR signal strength can be crucial in the
decision of Teff vesus Treg differentiation with remarkable consequences on clinical outcome.
key words: weed pollen allergens
Contact / E-Mail:
[email protected]
- 124 -
Multi-sensitization to hymenoptera venoms
Double sensitization to both, Apis mellifera and Vespula ssp. venom is common in up to 59% of
the European hymenoptera venom allergic patients. In Brazil, Polistes sp. and Polybia paulista
pose the major risk. Reports about double sensitization involving Apis mellifera and Solenopsis
are rare, and there is nothing described about multi-sensitization to insects.
Nine patients with anaphylactic reactions and sensitization to honeybee, wasp and fire ant
were tested by ImmunoCap, skin prick test (SPT), dot blot (DB) and western blotting (WB)
using commercial extracts of Apis mellifera, Polistes sp. and Solenopsis as well as Polybia
paulista venom extract produced by our group.
All patients were positive to four venoms in DB and WB. Four patients presented ImmunoCAP
<0.35 kUA/l for one or two venoms. In WB, the patients recognized multiple IgE-reactive
bands in each venom extract. Apart from homologous molecules, new allergens unique for
specific venoms were identified presenting distinct molecular masses not present in the other
sources.
This is the first report of multi-sensitization to four hymenoptera insect venoms. Next steps are
to produce recombinant species-specific allergens and evaluate them by component-resolved
diagnostics.
Poster Presentation
(1) Laboratory of Clinical Immunology and Allergy-LIM60, Division of Clinical Immunology and
Allergy, Department of Medicine, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
(2) Institute for Investigation in Immunology (iii), INCT, Sao Paulo, Brazil
(3) Division of Allergy, Clinics Hospital of School of Medicine, University of Sao Paulo, Sao
Paulo, Brazil
(4) Laboratory of Immunology, Heart Institute (InCor), LIM19, University of Sao Paulo, School
of Medicine, Sao Paulo, Brazil
(5) Institute of Biosciences of Rio Claro, University of Sao Paulo State (UNESP), Rio Claro, Brazil
(6) Department of Molecular Biology, Division of Allergy and Immunology, University of
Salzburg, Salzburg, Austria
Abstract 95
Karine MARAFIGO DE AMICIS (1,2,6); Alexandra SAYURI WATANABE (2,3); Clovis Eduardo
GALVAO (2,4); Daniele DANELLA FIGO (1,2); José Roberto APARECIDO DOS SANTOS-PINTO
(2,5); Mario Sergio PALMA (2,5); Fábio FERNANDES MORATO CASTRO (1,2,3); Jorge KALIL
(1,2,3,4); Fatima FERREIRA–BRIZA (6); Gabriele GADERMAIER (6); Keity SOUZA SANTOS
(1,2);
Acknowledgements
For the financial support of Fundação de Amparo à Pesquisa (FAPESP) and Conselho Nacional
de Desenvolvimento Científico e Tecnológico (CNPq) from Brazil.
Contact / E-Mail:
[email protected]
- 125 -
Poster Presentation
Abstract 96
Beside Der p 1 and Der p 2, also other house dust
mite allergens have high allergenic activity
Yvonne RESCH(1), Mira ŠILAR(2), Peter KOPAČ(2), Mihaela ZIDARN(2), Kuan-Wei CHEN(1),
Wayne THOMAS(3), Peter KOROŠEC(2), Mitja KOŠNIK(2), Rudolf VALENTA(1) and Susanne
VRTALA(1,4)
for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna,
Austria;
(2) University Clinic of Respiratory and Allergic Diseases Golnik, Golnik, Slovenia;
(3) Telethon Institute for Child Health Research, University of Western Australia, Perth,
Australia;
(4) Christian Doppler Laboratory for the Development of Allergen Chips, Medical University of
Vienna, Austria
Introduction: Der p 1 and Der p 2, the two major allergens in house dust mites (HDMs), have
been extensively studied, however, little is known about their allergenic activity in comparison
to other HDM allergens.
Methods: Seven important HDM allergens (Der p 1, Der p 2, Der p 5, Der p 7, Der p 10, Der
p 21 and Der p 23) were studied in regard to their IgE-binding frequency, the levels of IgE
directed to the allergens as determined by Streptavidin ImmunoCAPs and their allergenic
activity in CD63 based basophil activation tests, using sera from 30 clinically well-characterized
HDM-allergic Slovenian patients.
Results: Although Der p 1 and Der p 2 were the most frequently recognized allergens
(90%) and bound the highest levels of allergen-specific IgE (mean: 8.59 kU/L and 7.73
kU/L respectively) in the tested patients, they were not the most potent allergens in regard
to basophil activation. In fact, the newly identified major allergen Der p 23 (IgE-binding
frequency: 83%) induced the strongest basophil activation in sensitized patients, although
the allergen-specific IgE levels were low (mean: 2.61 kU/L). Interestingly, Der p 5, a mid-tier
allergen (IgE-binding frequency: 37%) showed the third highest IgE levels (mean: 4.18 kU/L)
and the second strongest basophil activation.
Conclusion: Der p 1 and Der p 2 were described as the most important allergens in HDM
allergy, however, other allergens additionally contribute strongly to the allergic symptoms in
sensitized patients.
Acknowledgements
This work was supported by grants F4602 and F4605 of the Austrian Science Fund (FWF),
Thermofisher, Uppsala, Sweden and the Christian Doppler Research Association, Austria.
Contact / E-Mail:
[email protected]
- 126 -
Lukas EINHORN(1,2), Judit FAZEKAS(1,2), Martina MUHR(1,2), Alexandra SCHOOS(1,2), Lucia
PANAKOVA(3), Krisztina MANZANO-SZALAI(1), Kumiko OIDA(1,4), Josef SINGER(2), Erika
JENSEN-JAROLIM(1,2)
IgE-based diagnosis has an overall lower clinical impact in veterinary medicine, possibly due
to a lack of high-quality IgE detection reagents for diverse species. Therefore, we aimed to
produce recombinant canine, feline and equine alpha chains of FcepsilonRI-alpha for highaffinity IgE detection in dogs, cats and horses to improve the specificity and spectrum of
diagnostic IgE tests in animals.
Combined with a custom SV40_Neo mammalian expression vector the Flag-tagged
FcepsilonRI-alpha fusion proteins of canine, feline and equine were expressed in CHO-DUKX
B11 cells. 384 clones of each species were selected according their productivity and quality
by ELISA and Immunoblot and purified via anti-FLAG M2 affinity gel. The purified recombinant
products were correctly folded as determined by CD-spectroscopy. Immunoblot and ELISA
assays verified integrity of the recombinant alpha chains. The recombinant proteins detected
allergen-specific serum IgE of the relevant species, but also showed crossreactivity to other
species including humans.
We here accomplished the expression of canine, feline and equine alpha chains for IgE
detection in these species. These tools will improve IgE-diagnosis in veterinary allergology and
comparison of sensitization profiles in humans and their animals.
Poster Presentation
Vienna, Medical University Vienna and University Vienna, Austria
(2) Comparative Immunology and Oncology, Institute for Pathophysiology and Allergy
Research, Center of Pathophysiology, Infectiology and
Immunology, Medical University of Vienna, Austria
(3)… Clinical Department of Small Animal Internal Medicine, University of Veterinary Medicine
Vienna, Austria
(4)… Laboratory of Veterinary Molecular Pathology and Therapeutics, Tokyo University of
Agriculture and Technology, Japan
Abstract 97
Expression of recombinant canine, feline and equine
FcepsilonRI-alpha chains for improved IgE profiling
in these species
Acknowledgements
Sources of funding:
Austrian Science Fund project SFB F4606-B19 and FWF grant P23398-B11. L. E. was supported
by the MCCA-PhD program W 1248-B13, J.S. and J.F. by W1205-B09.
Contact / E-Mail (of first author):
[email protected]
- 127 -
Abstract 98
High density IgE recognition of the major grass
pollen allergen Phl p 1 revealed with single chain
IgE antibody fragments obtained by combinatorial
cloning
Christoph MADRITSCH(1), Elisabeth GADERMAIER(1), Uwe RODER(2), Christian LUPINEK(1),
Rudolf VALENTA(1) and Sabine FLICKER(1)
Poster Presentation
(1) Division of Immunopathology, Department of Pathophysiology and Allergy Research,
Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna,
(2) GE Healthcare Europe GmbH, Freiburg, Germany
The timothy grass pollen allergen Phl p 1 belongs to the group 1 of highly cross-reactive
grass pollen allergens with a molecular weight of approximately 25-30kDa. Group 1 allergens
are recognized by more than 95% of grass pollen allergic patients. We investigated the IgE
recognition of Phl p 1 using allergen-specific IgE-derived single chain antibody fragments
(IgE-ScFvs) isolated from a combinatorial library constructed from PBMCs of a grass pollen
allergic patient. IgE-ScFvs reacted with recombinant Phl p 1 and natural group 1 grass pollen
allergens. Using synthetic Phl p 1-derived peptides the binding sites of two ScFvs were mapped
to the N-terminus of the allergen. In surface plasmon resonance experiments (SPR) they
showed comparable high affinity binding to Phl p 1 as a human IgE-derived complete antibody
recognizing the allergens’ C-terminus. In a set of SPR experiments simultaneous allergen
recognition of all three binders was demonstrated. Even in the presence of the three binders,
allergic patients’ polyclonal IgE reacted with Phl p 1 indicating high density IgE recognition of
the Phl p 1 allergen. Our results show that multiple IgE antibodies can bind with high density
to Phl p 1, which may explain the high allergenic activity and sensitizing capacity of this
allergen.
Acknowledgements
Funding Sources: This study was supported by grants F4607 and F4605 of the Austrian Science
Fund (FWF).
Contact / E-Mail:
[email protected]
- 128 -
Bernhard KRATZER(1), Alina NEUNKIRCHNER(1,2), Winfried F. PICKL(1,2)
(1) Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical
(2) Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna,
Austria.
Poster Presentation
Allergies affect more than 25% of individuals in our population. However, experimental animals
able to present the immunodominant peptides of human-relevant aeroallergens are scarce,
making the investigation of novel strategies for allergy treatment or prevention difficult. To
overcome these limitations, we created a pair of novel cassette vectors for tissue-specific
expression of HLA-DR molecules in mice. The peptide binding domains of HLA-DRA*01:01
and HLA-DRB1*07:01 were chimerized to the corresponding constant domains of H-2 IEd
alpha and beta. HLA sequences were flanked by unique Not I and Cla I restriction enzyme
sites to enable rapid, directed exchange for other allelic sequences. HLA-DRA and –DRB1
variable sequences are flanked by ≥ 6kb of 5’- and 3’-genomic sequences, to conserve unique
promoter/enhancer elements. Functional evaluation of cassette-encoded transgenes revealed
MHC class II transactivator-dependent HLA expression, which was functionally confirmed in
proliferation assays using allergen-specific T cells. The novel HLA::IE cassette vectors will
contribute to the quick and facile creation of a collection of HLA transgenic mice, to better
understand the mechanisms of immune-mediated diseases such as allergies and to evaluate
novel immunotherapeutic concepts.
Abstract 99
Generation of new cassette vectors for the targeted
presentation of human-relevant antigens (allergens)
in humanized mouse models
Acknowledgements
Supported by the Austrian Science Fund (FWF) project DK-W1248-B13 (as part of the PhD
program Molecular, Cellular and Clinical Allergology, MCCA of the Medical University of Vienna),
SFB F46909-B19 and Biomay AG.
Contact / E-Mail:
[email protected]
- 129 -
Poster Presentation
Abstract 100
Identification and characterization of natural
adjuvants in birch pollen
Dagmar WERNER, Birgit NAGL, Barbara BOHLE
IgE-mediated allergy is a hypersensitivity reaction of the immune system to normally harmless
antigens which is due to an aberrant Th2-dominated immune response. 25% of urban
population suffer from allergic disorders and 1/4 reacts to birch pollen(BP). The major BP
allergen Betv1 is recognized by 95% of birch pollen-allergic patients, whereas less than 50%
react to the minor allergens Betv2, 3, 4, 6 and 7. By expanding BP-specific T-cell clones(TCCs)
from the peripheral blood of BP-allergic patients we found BP extract-specific TCCs that were
not specific for any of the known allergens in BP. So far, 17 BP extract-specific TCCs could be
expanded. After stimulation with BP, signature cytokines for Th2 and Th1 were measured in
supernatants of these TCCs. 59% belonged to the Th0, 35% to the Th1 and only 1% to the
Th2 subset. This led to the assumption that there are distinct proteins in BP which induce a
Th0/1-like response rather than a Th2-like reaction. The aim of this study is to identify and
characterize those proteins. BP proteins were separated with size exclusion chromatography.
BP extract-specific TCCs will be tested with the individual fractions. In parallel, the fractions
will be subjected to endo-lysosomal degradation assays to draw conclusions on their
immunogenicity. It has been demonstrated that proteins with higher resistance to endolysosomal proteolysis are more immunogenic. After identification and isolation of candidate
proteins they will be analyzed in more detail. These Th0/1 subset supporting BP proteins may
represent natural adjuvants which could be supplemented to vaccines for immunotherapy of BP
allergy.
Acknowledgements
Supported by the Austrian Science Fund project W1212 and SFB F4610, CD Laboratory for
Immunmodulation and Biomay AG
Contact / E-Mail:
[email protected]
- 130 -
Dominika POLAK, Birgit NAGL, Claudia KITZMÜLLER, Barbara BOHLE
Poster Presentation
Although large numbers of neutrophils are present in late-phase reactions, their role in allergic
disorders is not well understood. These professional phagocytes can be activated to express
MHCclassII molecules by stimulation with certain cytokines, chemokines and bacterial factors,
such as GM-CSF, TNF-alfa, IL-8, IFN-gamma and LPS. Some studies have even shown that
murine neutrophils are able to process and present antigens to CD4+T-cells.
The aim is to assess whether human neutrophils act as antigen-presenting cells for allergenspecific T-cells.
The isolation of pure neutrophils from human blood was established and they were assessed
for the expression of MHCclassII and co-stimulatory molecules under different conditions by
flow cytometry. Surface binding, internalization and intracellular degradation of fluorescencelabelled Bet v 1 by neutrophils were compared with monocytes. Endolysosomal proteases were
isolated from neutrophils and monocytes. Finally, neutrophils and monocytes were used as
antigen presenting cells for Bet v 1-specific T-cell lines.
So far, we found that the mixture of IL-3,GM-CSF and IFN-gamma enhanced the expression
of HLAclassII on neutrophils. Neutrophils internalized Betv1 with a different kinetic than
monocytes. Endolysosomal extracts of neutrophils were produced and will now be used for
degradation assays of Betv1. The resulting peptides will be analysed by mass spectrometry.
In first experiments with Betv1-specific T-cell lines neutrophils plus Betv1 induced T-cell
proliferation.
Our data provide evidence that neutrophils can activate allergen-specific T-cells. Further
experiments are on the way.
Abstract 101
The role of neutrophils in IgE-mediated allergy
Acknowledgements
Supported by the Austrian Science Funds, project W1248 and SFB F4610.
Contact / E-Mail:
[email protected]
- 131 -
Poster Presentation
Abstract 102
Cor a 8 displays reduced stability upon heat and
digestion treatment
Pawel DUBIELA(1), Sabine PFEIFER(1), Merima BUBLIN( 1, 2), Christine HAFNER(1),
Karin HOFFMANN-SOMMERGRUBER(1)
Austria; 2Karl Landsteiner Institute for Dermatological Research, St. Poelten, Austria
Background and Aim: So far, 10 hazelnut allergens have been identified, among those the
ns lipid transfer protein, Cor a 8. The aim of the study is to purify and characterize the
physicochemical and allergenic properties of Cor a 8.
Methods: nCor a 8 was purified from raw hazelnuts by precipitation and chromatographical
steps. The protein was identified by N-terminal sequencing and mass spectrometry.
Immunological and physicochemical experiments were performed.
Results: Mass spectrometry analysis provided 9.475 kDa for purified nCor a 8 which
corresponds to the theoretical mass of 9.468 kDa (database access nr: 9QATH2). The intact
N-terminus was verified by Edman-degradation. In stability assays purified Cor a 8 displayed
reduced stability against enzymatic and heating treatment as compared to Pru p 3. Three out
of six sera had IgE predominantly recognizing linear epitopes as compared to 3 sera which had
IgE specific for conformational epitopes. In RBL assays Cor a 8 induced mediator release. Upon
addition of hazelnut lipids this response was remarkably increased.
Conclusions: Cor a 8 was purified from extract, displaying the physicochemical properties
different to Pru p 3. In cellular assays the allergenic activity of Cor a 8 was considerably
increased when adding hazelnut lipids, thus showing the impact of food matrix on the
allergenicity of a single food protein.
Acknowledgements
Supported by grants SFB F4603 and W1248 (Austrian Science Fund) to K. HoffmannSommergruber and P. Dubiela, respectively.
Contact / E-Mail:
[email protected]
- 132 -
Ulla KNACKMUSS(1), Wilfried POSCH(1), Marion STEGER(1), Michael BLATZER(1), Kristian
PFALLER(2), Cornelia LASS-FLÖRL(1), Doris WILFLINGSEDER(1)
(1) Division of Hygiene and Medical Microbiology, Schöpfstrasse 41, Innsbruck, Austria,
(2) Division of Embryology and Histology, Innsbruck Medical University, Müllerstrasse 59,
Innsbruck, Austria
Poster Presentation
The immune response to viral infections comprises complex interplays between the virus and
the immune system and aims in eradication of the pathogen with least damage to the host.
Dendritic cells (DCs), which are essential for the generation of a protective antiviral immune
response, are exploited by the viruses to evade innate and adaptive immunity. When HIV
enters the body, virus becomes immediately opsonized with complement fragments which
should help to eradicate the virions by the innate immune system. We earlier showed that
differential opsonization of HIV significantly modulates antigen capture and presentation by
DCs (Wilflingseder et al, 2007; Posch et al, 2012). We are now interested in investigating
the initial signaling events in DCs upon exposure using differentially opsonized HIV in more
detail to identify novel therapeutical targets. We here found that significantly higher amounts
of complement-opsonized HIV (HIV-C), which induces a potent specific CD8+ T cell response
via DCs, bound to DCs and HIV-C was able to overcome innate DC restriction in contrast
to non-opsonized HIV (HIV). Additionally, HIV-C signaled via Rac1 and caused prolonged
phosphorylation of ERK1/2 and JNK/SAPK, while HIV activated RhoA and did not induce MAPKs
in DCs. Our data demonstrate the importance to distinguish the initial cellular events after
attachment/internalization of differentially opsonized HIV and might provide a promising novel
strategy to tackle HIV-1 infection.
Abstract 103
HIV opsonization modulates DC signaling
Acknowledgements
We would like to thank our technician Karolin Lechleitner and the FWF (P24598 to DW, P25389
to WP) and the ÖNB (Project 14875).
Contact / E-Mail:
[email protected]
- 133 -
Poster Presentation
Abstract 104
Interleukin-2/anti-interleukin-2 antibody complexes
expand T regulatory cells and protect against
allergen-induced airway hyperreactivity
Alina NEUNKIRCHNER(1,2), Daniela WOJTA-STREMAYR(1,2), Klaus G. SCHMETTERER(2),
Lukas MAGER(2) Victoria REICHL(1,2), Edward ROSLONIEC(3), Ronald NAUMANN(4), Gerhard
DEKAN(5), Beatrice JAHN-SCHMID(6), Barbara BOHLE(1,6) and Winfried F. PICKL(1,2)
(1) Christian Doppler Laboratory for Immunomodulation, Center for Pathophysiology,
(2) Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical
(3) Veterans Affairs Medical Center, Memphis, TN, USA
(4) Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany
(5) Institute of Clinical Pathology, Medical University of Vienna, Vienna, Austria
T-cells play a key role in the development and maintenance of allergic diseases and thus
represent a promising target for therapeutic interventions. Evidence from SIT studies suggest
that regulatory T-cells (Treg) might counterbalance the Th2-biased immune response. We
here created double trangenic (tg) allergy mice expressing a human TCR specific for the major
mugwort (Artemisia vulgaris) pollen allergen Art v 1 and HLA-DR1 to study the response to
the human-relevant aero-allergen in vivo. After allergen-specific sensitization, only double tg
allergy mice, but not single tg or wt control mice showed enhanced airway-hyperreactivity
(AHR) upon challenge, which was associated with airway and lung inflammation. Significantly,
treatment of allergy mice with three daily i.p. injections of IL-2/anti-IL-2 mAb complexes
induced a 6-fold increase of CD25+Foxp3+ Treg among CD3+CD4+T-cells in peripheral blood
(17.9±6.2% compared to 3.1±1.4%). Furthermore, expansion of Treg by IL-2/anti-IL-2 mAb
complexes before sensitization prevented mice from allergen-induced AHR upon challenge
and significantly reduced Art v 1-specific serum IgE, when compared to sham-treated mice.
In summary, expansion of Treg by IL-2/anti-IL-2 mAb complexes seems to be a promising
strategy to interfere with allergic diseases.
Acknowledgements
Support: Austrian Science Fund SFB-F4609-B19 & Christian Doppler-Research Association and
Biomay AG
Contact / E-Mail:
[email protected]
- 134 -
Guido A. GUALDONI(1), Katharina A. MAYER(1), Johanna M. GOSTNER(2), Dietmar FUCHS(3),
Gerhard J. ZLABINGER(1)
(1) Institute for Immunology; Center for Pathophysiology, Infectiology and Immunology,
(2) Division of Medical Biochemistry, Medical University of Innsrbuck
(3) Division of Biological Chemistry, Medical University of Innsbruck
Poster Presentation
Resveratrol is a polyphenol compound found in a variety of nutrients and has been shown to
have immunomodulating, anti-cancerogenic and cardioprotective effects. The regulation of the
rate limiting enzyme of inflammatory tryptophan metabolism, indolamine-2,3-dioxygenase
(IDO), has been proposed to be involved in resveratrol’s biological effects. These observations,
however, rely on in vitro findings and animal studies. In order to analyze resveratrol’s IDOmodulation in humans, we performed a pilot study including 10 healthy volunteers with oral
administration of 5g resveratrol (resveratrol n=8, placebo n=2). Plasma levels of tryptophan
and kynurenine were analyzed to assess IDO activity. After resveratrol application, tryptophan
levels dropped markedly within 2.5h (p<0.001) and 5h (p<0.001). Kynurenine levels were
slightly elevated at 2.5h which resulted in an 1.33 and 1.30 fold increase in the kynurenine/
tryptophan ratio at 2.5h (p<0.01) and 5h (p<0.01), respectively. The present study provides
evidence for a profound modulation of tryptophan metabolism after oral resveratrol intake.
Since IDO has been shown to play a crucial role in immunity, cancer development and
regulation of vascular tone, the modulation of this enzyme might be involved in resveratrol’s
biological effects.
Abstract 105
Resveratrol intake enhances indolamine-2,3dioxygenase activity in humans
Acknowledgements
The authors thank Dr. Michael Wolzt for support in the performance of the study.
Contact / E-Mail:
[email protected]
- 135 -
Poster Presentation
Abstract 106
The CD58-CD2 axis is the primary costimulatory
pathway in human CD28 negative CD8 T cells
Judith LEITNER(1), Dietmar HERNDLER-BRANDSTÄTTER(2), Beatrix GRUBECKLOEBENSTEIN(2), Gerhard ZLABINGER(1), Peter STEINBERGER(1)
(1) Institute for Immunology, Center for Physiology, Pathophysiology and Immunology, Medical
(2) Austrian Academy of Sciences, Institute for Biomedical Aging Research, Immunology
Division, Innsbruck, Austria
Aging and repeated antigen encounter eventually leads to a state known as immune
senescence. Loss of CD28, the most potent costimulatory receptor on human T cells, is
generally regarded to be a main predictor of biological aging of the human immune system.
Besides CD28 there are numerous additional receptors that costimulate T cell activation. Little
is known on the role of these costimulatory ligands in the function of CD28- T cells.
We have examined such alternative pathways regarding their functional role in CD28-CD8+ T
cells.
We activated CD28-CD8+ T cells from elderly individuals in the presence of the most important
costimulatory ligands CD58, 41BBL, ICOSL, CD166, CD70, OX40L, GITRL, CD54.
Our study showed that most costimulatory molecules have low capacity to activate CD28- T
cells, whereas the engagement of the CD2 molecule by its ligand CD58 strongly costimulated
proliferation, cytokine production and effector function in this T cell subset. CD58 is broadly
expressed on antigen presenting cells including dendritic cells. Blocking CD58 mAb greatly
reduced the response of human CD28-CD8+ T cells to allogeneic DC as well as to viral
antigens. Our results clearly identify the CD58/CD2 axis as the primary costimulatory pathway
for CD8 T cells that lack CD28.
Acknowledgements
Supported by a grant from the ONB12731 to PS and Theodor Körner Fond to JL.
Contact / E-Mail:
[email protected]
- 136 -
Markus STEINER(1), Thomas HAWRANEK(2), Michael SCHNEIDER(3), Andrea HARRER(2),
Jutta HOREJS-HOECK(1), Fatima FERREIRA(1), Martin HIMLY(1)
(2) Paracelsus Medical University, Salzburg, Austria
(3) Bühlmann Laboratories AG, Schönenbuch, Switzerland
Poster Presentation
Human basophils represent well-known allergic effector cells. However, an involvement of
basophils in innate immunity regulated by TLRs has been hypothesized and TLR signaling has
been postulated to influence the IgE-mediated pathway. We thus asked the question whether
basophils derived from allergic patients differ from basophils of non-allergic donors regarding
TLR stimulation. Basophils of birch pollen-, mite-, and non-allergic donors were purified via
density centrifugation and negative magnetic cell sorting. TLR-1, 2, 4, and 6 expression levels
were analyzed by flow cytometry. Up-regulation of CD203c and cytokine release of basophils
after incubation with ligands for TLR-1/2, 2/6, and 4 were investigated using a multiplex
assay for IL-4, 6, 8, 23, IFN-gamma, MCP-1, and TNF-alpha. Basophils of allergic and nonallergic donors expressed similar amounts of TLR-1 and 2, whereas TLR-4 seemed to be less
prominent in mite-allergic donors. Surprisingly, IL-8 release of basophils of mite-allergic
donors was higher upon TLR-4 stimulation. In contrast, TLR stimulation did not alter CD203c
surface expression and only minor differences in IL-4 release were observed in all groups. In
conclusion, these results point towards a possible link between allergy and TLR-signaling.
Abstract 107
Basophils from house dust mite-allergics show an
altered TLR profile from birch pollen- or non-allergic
individuals
Acknowledgements
The study was funded by grant P18820-B13 of the Austrian Science Funds (FWF).
Contact / E-Mail:
[email protected]
- 137 -
Poster Presentation
Abstract 108
The soluble cytoplasmic tail of CD45 (ct-CD45)
induces quiescent anergy in human T cells
Alexander PUCK, Maria SEYERL, Stefan HOPF, Otto MAJDIC, Gerhard
ZLABINGER, Judith LEITNER, Peter STEINBERGER, Johannes STÖCKL
Institute of Immunology, Center for Pathophysioloy, Infectiology and Immunology,
Medical University of Vienna, Vienna, Austria.
The cytoplasmic tail of CD45 (ct-CD45) is proteolytically cleaved and released upon
activation of human phagocytes. The soluble ct-CD45 was found to act on T cells as an
inhibitory, cytokine-like factor that reduces T cell proliferation. In this study, we
aimed to elucidate the molecular mechanisms acting within T cells, upon ct-CD45
binding. Here, we demonstrate that ct-CD45 induces a novel form of anergy in human
peripheral blood T cells. Ct-CD45 inhibited the function (proliferation, cytokine
production) of human T cells and rendered the cells hyporesponsive to restimulation,
which was reversible by exogenous IL-2 or IL-7. However, microarray analysis did not
indicate induction of any classical anergy-associated genes. Instead, we found
induction of Schlafen family member 12 (SLFN12) and of Krueppel-like factor 2 (KLF2).
When we analyzed the expression patterns of cell cycle regulatory factors, we found
inhibition in the induction of cyclin D1 while other cyclins were unaltered. In
summary, ct-CD45 triggers an anergy program in T cells, which is reversible by
exogenous IL-2, acting independently of classical anergy factors. From our data, the
inhibition of cyclin D1 suggests a cell cycle arrest in the early G1 phase, thus
making it distinct from canonical T cell anergy.
Acknowledgements
We acknowledge Claus Wenhardt, Margarethe Merio, Petra Waidhofer-Söllner, Petra Cejka
and Jens Gerwien for their expert technical assistance.
Contact / E-Mail:
[email protected]
- 138 -
Ralf SCHMIDT(1), Franz RATZINGER(1), Sabrina JUTZ(2), Peter STEINBERGER(2), Winfried F.
PICKL(2) and Klaus G. SCHMETTERER(1)
(1) Department of Laboratory Medicine, Medical University of Vienna, Austria
(2) Institute of Immunology, Medical University of Vienna, Austria
Poster Presentation
The anti-malarial drugs chloroquine and hydroxy-chloroquine have immunomodulatory potency
which is therapeutically harnessed in rheumatic diseases. However, the exact mechanisms of
action on immune cells have not been fully described. Consequently, we assessed the influence
of chloroquine on highly purified human CD4+ T-cells. T-cells were pre-incubated with
chloroquine at concentrations of up to 10 µM which leads to intracellular accumulation of drug
levels comparable to oral therapy in rheumatic diseases. Following activation with anti-CD3/
anti-CD28 agonistic antibodies, chloroquine treated T-cells were suppressed in proliferation
as well as secretion of cytokines. These effects were due to specific inhibition of activation
since no decrease in cellular viability could be detected. In restimulation experiments, we
determined that the effects of chloroquine were reversible after removal of the substance.
Using Jurkat reporter cell lines expressing GFP under control of either the NFAT, NF-kB or
AP-1 promoter, we observed that chloroquine specifically inhibited AP-1 promoter activity. In
conclusion, we describe immunosuppressive functions of chloroquine on purified CD4+ T-cells
and propose that inhibition of AP-1 activity is the main molecular mechanism of this effect.
Abstract 109
The anti-malarial drugs chloroquine and hydroxychloroquine show suppressive potency on purified
human CD4+ T-cells
Contact / E-Mail:
[email protected]
- 139 -
Poster Presentation
Abstract 110
STAT3 governs granzyme B and IL-10 production in
CD4+ T-cells
Klaus G. SCHMETTERER(1,2), Alina NEUNKIRCHNER(1), Daniela WOJTA-STREMAYR(1) Judith
LEITNER(1), Peter STEINBERGER(1), and Winfried F. PICKL(1)
STAT3 is a key integrator of signals transmitted from cell surface immune receptors. To assess
the effects of STAT3 activation in human T-cells, a constitutively active mutant of STAT3, i.e.
STAT3C, was cloned into an IRES-GFP harboring retroviral vector. STAT3C-transgenic CD4+
T-cells showed clear-cut transgene expression and phenotypically displayed an effector T-cell
surface phenotype. Besides, a significant up-regulation of intracellular granzyme B levels
could be observed. STAT3C+ T-cells were hypo-responsive following stimulation. They further
displayed a distinct cytokine secretion profile including a significant increase in IL-10 and a
reduction of IL-2, IFN-gamma and IL-13 secretion. Of note, STAT3C+ T-cells activated via
CD3/CD2 significantly suppressed effector T-cell proliferation. Mechanistically, suppression
was dependent on the release of granzyme B and concomitant apoptosis of effector T-cells.
Our observations are further substantiated by the finding that peripheral blood Tr1 cells reveal
activation-induced hyperphosphorylation of STAT3. Furthermore, exposure of Tr1 cells to a
STAT3 inhibitor could partially revert their hyporesponsiveness. This indicates a clear-cut
relation between activation of STAT3 and the acquisition of a tolerogenic program.
Contact / E-Mail:
[email protected]
- 140 -
Harald SCHWARZ, Maria SCHMITTNER, Albert DUSCHL, Jutta HOREJS-HOECK
University of Salzburg, Department of Molecular Biology, Hellbrunner Str. 34, A-5020 Salzburg
Poster Presentation
Commercially available recombinant proteins are often produced in E. coli. Most suppliers
guarantee less than 1 endotoxin unit (EU) of contamination in their products. We analysed
several recombinant proteins for their endotoxin content and found endotoxin contaminations
in the same range as stated in the data sheets, but also some that were higher. To analyse
whether these low levels of contamination have immunomodulatory effects, we stimulated
different human immune cells with very low concentrations of lipopolysaccharide (LPS;
ranging from 0.002 – 2 ng/ml). We show that primary human CD1c+ dendritic cells especially
can be activated by minimal amounts of LPS. In more detail, 20 pg/ml LPS are sufficient to
significantly up-regulate the expression of IL-6 and IL-8, as well as the surface activation
markers CD40, CD80 and CD86. Notably, we found that the enhanced endotoxin sensitivity
of CD1c+ DCs was closely correlated to high CD14 expression levels observed in CD1c+ DCs
that have been cultured in medium for 24 hours. To avoid the generation of erroneous data,
we suggest different endotoxin detection assays to thoroughly screen recombinant proteins for
endotoxin contamination when working with immune cells that are highly sensitive to LPS.
Abstract 111
Endotoxin contaminations in recombinant proteins
activate primary human CD1c+ dendritic cells
Acknowledgements
We thank Andrei Medvedev and Douglas Golenbock for providing the TLR4, MD-2 and CD14
expression vectors.
Contact / E-Mail:
[email protected]
- 141 -
Poster Presentation
Abstract 112
Generation of a multi-parameter reporter T cell line
Sabrina JUTZ(1), Sandra ROSSKOPF(1), Judith LEITNER(1), Klaus SCHMETTERER(2), Katharina
GRABMEIER-PFISTERHAMMER(3), Peter STEINBERGER(1)
(1) Division of Immune Receptors and T cell activation, Institute of Immunology, Center for
Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
(3) Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology,
Activation of T cells occurs via a complex signaling network. The transcription factors AP-1,
NFAT and NF-kappaB play a central role in T cell activation and are required for cytokine
expression, T cell differentiation and proliferation. The aim of this work is to establish a
reporter T cell line enabling measurement of the activation of those three transcription factors
simultaneously. Three reporter constructs were generated with response elements for the
respective transcription factors and three different fluorescent proteins which do not overlap
in their spectra. To measure AP-1, NFAT and NF-kappaB activation, mCherry, eGFP and CFP
were used as reporter genes, respectively. The Jurkat cell line E6 was transduced with these
constructs and a stable single cell clone was established. Cocultivation of reporter cells with
T cell stimulator cells that trigger the TCR-complex led to an induction of AP-1, NFAT and NFkappaB. The use of T cell stimulator cells bearing CD58 or CD80 further increased reporter
gene expression. Moreover, this system can also be used to analyze inhibitory pathways e.g.
PD1/PDL1. In conclusion, our multi-parameter T cell line is a powerful tool to measure the
activation of the main signaling pathways in T cell activation.
Acknowledgements
Supported by FWF grant 21964-B20
Contact / E-Mail:
[email protected]
- 142 -
Franz RATZINGER(1), Helmuth HASLACHER(1), Wolfgang POEPPL(2), Gregor HOERMANN(1),
Johannes J KOVARIK(3), Sabrina JUTZ(4), Peter STEINBERGER(4), Heinz BURGMANN(2),
Wolfgang F PICKL(4) and Klaus G SCHMETTERER(1)
(2) Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical
(3) Clinical Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical
Poster Presentation
Advanced macrolides, such as azithromycin (AZM) or clarithromycin (CLM), are antibiotics with
immunomodulatory properties. Here we have sought to evaluate their in vitro influence on the
activation of CD4+ T-cells.
Isolated CD4+ T-cells were stimulated with agonistic anti-CD3/anti-CD28 monoclonal
antibodies in the presence of different macrolides. Cell proliferation, cytokine secretion of
supernatants and cell viability was assessed. Intracellular signaling pathways were evaluated
using reporter cell lines, FACS analysis, immunoblotting and in in vitro kinase assays.
AZM inhibited cell proliferation rate and cytokine secretion of CD4+ T-cells in a dose-dependent
manner. At therapeutic concentrations, no reduction of cell viability was observed. In contrast,
CLM showed only minor effects on T-cell function. Analysis of molecular signaling pathways
revealed that treatment with AZM reduced the phosphorylation of the S6 ribosomal protein, a
downstream target mTOR. In vitro kinase studies using recombinant mTOR showed that AZM
inhibited mTOR activity. In contrast to rapamycin, this effect was independent of FKBP12.
We show for the first time that AZM acts as immunosuppressive agent on CD4+ T-cells at
therapeutically relevant concentrations by inhibition of mTOR activity.
Abstract 113
Azithromycin suppresses CD4+ T-cell activation by
direct modulation of mTOR activity
Acknowledgements
The study was conducted in cooperation with the MedUni Wien Biobank facility. The project
was supported by grants of the Austrian Society for Laboratory Medicine and Clinical Chemistry
(ÖGLMKC); the Medical Scientific Fund of the Mayor of the City of Vienna [Grant 13040BGM,
14041BGM]; and the Austrian Science Fund [Grant SFB F4609]. None of the founder had
influence on any phase of this project.
Contact / E-Mail:
[email protected]
- 143 -
Poster Presentation
Abstract 114
The impact of NOD1 on IL-10 signaling
Theresa NEUPER, Albert DUSCHL and Jutta HOREJS-HOECK
University of Salzburg, Department of Molecular Biology, Salzburg, Austria
NOD1 was originally found to recognize the bacterial cell wall component iE-DAP. However, in
this study we show that NOD1 plays a novel role as intrinsic regulator of IL-10 signaling.
We demonstrate that silencing of NOD1 in human moDCs causes a significant increase in
IL-10 mRNA expression in response to IL-10, whereas the expression of CD86 was largely
suppressed. As IL-10 treated moDCs are an accepted model of tolerogenic DCs, we analysed
the role of NOD1 in these cells. We show that tolerogenic DCs lacking NOD1 produce lower
levels of IL-6 and IL-12. Moreover, in co-culture experiments tolerogenic DCs deficient for
NOD1 are more potent to induce IL-10 secretion by naïve CD4+ T cells, whereas IFN-gamma
release is unaffected. These findings suggest that NOD1 may counter-regulate the tolerogenic
potential of IL-10 stimulated DCs.
Analysis of regulatory proteins, which may be involved in NOD1-mediated modulation of IL-10
signaling revealed that specifically SOCS2 mRNA expression was clearly decreased in moDCs
lacking NOD1. Moreover, silencing of SOCS2 in moDCs does have similar effects on IL-10
targets as a lack of NOD1. Taken together, this study identifies NOD1 as a novel player in
modulating IL-10 signaling and suggests that SOCS2 may be involved in this process.
Acknowledgements
This project is supported by the Austrian Science Fund, FWF, grant number W1213.
Contact / E-Mail:
[email protected]
- 144 -
Johanna PRODINGER(1), Julia LOACKER(1), Ralf SCHMIDT(1) Franz RATZINGER(1), Sabrina
JUTZ(2), Peter STEINBERGER(2), Gregor HÖRMANN(1), Winfried F. PICKL(2) and Klaus G.
SCHMETTERER(1)
(1) Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
(2) Institute of Immunology, Medical University of Vienna, Vienna, Austria
Poster Presentation
Tryptophan metabolites such as kynurenine (KYN), 3-hydroxyanthranilic acid (3-OH-AA)
and picolinic acid (PA) are key mediators of immunosuppression by cells expressing the
tryptophan-catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). However, studies on the
influence of tryptophan metabolites on CD4+ T-cells have so far only focused on the effects of
KYN and 3-OH-AA. Consequently, we assessed the influence of PA on cell viability, proliferation,
cellular metabolism, cytokine secretion and production and up-regulation of surface markers
following in vitro activation with agonistic anti-CD3/anti-CD28 antibodies. In contrast to KYN
and 3-OH-AA, exposure of T-cells with PA did not affect cell viability, while proliferation and
metabolic activity was suppressed in a dose-dependent manner. T-cell functions requiring
protein synthesis, such as cytokine secretion and cell surface marker up-regulation, were not
or only weakly inhibited by PA. Restimulation experiments revealed that PA-exposure induced a
state of IL-2 resistant anergy. Phosphorylation of c-Myc at Ser62, was strongly reduced in PAexposed T-cells while more upstream signaling molecules were not affected. In conclusion, PA
mediates inhibition of cell cycle and metabolic activity while leaving protein production intact.
Abstract 115
The tryptophan metabolite picolinic acid suppresses
proliferation and metabolic activity of CD4+ T-cells
Contact / E-Mail:
[email protected]
- 145 -
Sparkling Science
Abstract 116
ALRAUNE - Allergy Research in Rural, Alpine and
Urban Networks
David SCHWARZENBACHER(1)*, Julia ZLOEBL(1)*, Teresa STEMESEDER(2), Eva
KLINGLMAYR(2), Edith OBERKOFLER(1), Gabriele GADERMAIER(2)
(1) HBLA Ursprung, Elixhausen, Austria
Students of HBLA Ursprung and BG Tamsweg work with scientists in an interdisciplinary
project to find possible correlations between the exposition to indoor allergens, different
lifestyle habits including physical exercise or diet, demographic data and the risk to develop
an allergic disease. Blood from 501 school children living in different geographic regions were
analyzed for IgE sensitization using ImmunoCAP ISAC microarrays. All participants collected
a dust sample from their home to investigate the concentration of various indoor allergens. In
order to evaluate the lifestyle, a questionnaire was created by scientists in co-operation with
students. Students of HBLA Ursprung were peer-to-peer teaching general aspects of allergic
diseases when visiting the schools. The project also focuses on transferring science to public.
Presentations and experiments for events in science communication like “Lange Nacht der
Forschung” or “Science Day” were prepared and the team will take part in a “Science Slam”.
Preliminary results showed a very high IgE sensitization rate of 53% among all participants
with grass pollen, house dust mites and birch pollen as major allergen source and statistical
analysis will enable identification of factors influencing allergic diseases.
Acknowledgements
We thank our project partners from the University of Salzburg, University of Applied Sciences
Salzburg, Paracelsus Medical University Salzburg and University of Education Salzburg. The
study was funded by Sparkling Science, a program of the Federal Ministry of Science, Research
and Economy, Vienna, Austria.
Contact / E-Mail:
[email protected]; [email protected]
- 146 -
- 147 -
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of Nucleic Acids
REV 3.2
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*Single Cell analysis requires amplification prior to analysis on the nCounter System.
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Abstract Book - Österreichische Gesellschaft für Allergologie und

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