Senasta forskningsrön i celiaki

Senasta forskningsrön i
celiaki
Markku Mäki
Tammerfors Universitet och
Universitetssjukhuset i Tammerfors,
Tammerfors, Finland
Tammerfors 30.11.2007
Coeliac
CoeliacDisease
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Classical presentations of coeliac disease
Coeliac
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Coeliac disease
Daily ingested wheat-, rye-, and barley-induced manifest mucosal lesion in
genetically susceptible individuals (DQ2 +ve or DQ8 +ve)
gluten
on
off
Clinically silent coeliac disease
manifest mucosal lesion
Gastrointestinal symptoms
mild –severe
Risk groups
Type I diabetes
Thyroid disease
Sjögren’s syndrome
Down’s syndrome
IgA deficiency
Symptoms and signs of malabsoption
Extraintestinal manifestations
dermatitis herpetiformis, osteopenia and osteoporosis, dental enamel defects,
peripheral and central nervous system invovement, liver diseases, reproductive
system involvement, malignancies
Coeliac
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Diagnosis of coeliac disease
High index of suspicion
Classical symptoms and signs
Biopsy
Minor symptoms
Extraintestinal manifestations
Antibody case finding
Risk groups
Coeliac
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-EMA
-tTG-ab
-AGA
(deamin
peptide)
-whole
blood
rapid test
Membership development during 1976-2006
in the Finnish Coeliac Society
M embe rship development during 1976-11/2006
in the Finnish Coeliac Associations
17 003
18000
15 470
16000
13 688
14000
11 030
12000
9 657
10000
7 415
8000
5 792
6000
6 332
4 742
4000
1 950
2000
980
50
0
1976
1980
1985
1990
1992
1994
1996
1998
2000
2002
2004
11/2006
Schoolchildren
Blood sampling in
1994
Mäki et al., NEJM 2003
n=3,654
EMA and/or tTG +
n=56
Serum
autoantibody
testing in
2001
IgA-EMA+
IgA-EMA+ IgA-EMA- IgA-EMA -, IgG-EMA +
IgA-tTG+
IgA-tTG-
n=50
n=1
IgA-tTG+ IgA-tTG -, IgG-tTG+
Symptom detected CD Screen detected CD
Smallbowel
biopsies
n=27
n=10
IgA-EMA and tTG+
IgG-EMA and tTG+
n=25
Celiac trait
IgA-EMA+ n=7
IgA-EMA+ n=10
IgA-tTG+ n=9
IgA-tTG+ n=9
n=2
DQ2+ n=7
DQ2+ n=22
DQ2+ n=7
DQ8+ n=3
DQ8+ n=3
DQ2/DQ8+ n=1
DQ2/DQ8+ n=1
DQ2 and DQ8–n=1
DQ2 and DQ8- n=1
Biopsy proven CD
n=10
IgG-EMA and tTG+
n=1
HLA
Normal on biopsy Not biopsied
n=9
IgA-EMA and tTG+
n=9
n=3
n= 2
1:99
1:67
DQ2+ n=10
’Mini-Finland’1978-80
Clinical prevalence of CD
Total prevalence of CD
95 % CI
Coeliac
CoeliacDisease
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0.03%
1.1%
0.8 -1.3
’Health 2000’
2000-01
0.52%
2.0%
1.6 –2.3
Lohi et al., Aliment Pharm Therap, 2007;26:1217-25.
CD
Type 1 DM
Coeliac
CoeliacDisease
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Lohi et al., Aliment Pharm Therap, 2007;26:1217-25.
Prevalence of coeliac
disease in Finland
•CHILDREN
•ADULTS
Coeliac
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1.5 %
2.0 %
Lower economic status and
inferior hygienic environment may
protect against celiac disease
Kondrashova et al. Ann Med 2007, iFirst Article, 1-9
(epub ahead of print)
Finland 1:100
Russian Karelia 1:500
Coeliac
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Do DIY health tests work?
We ask the experts for their verdicts.
Unable to get an appointment with your GP?
Too embarrassed by your symptoms?
It's not surprising many of us now turn to
home testing kits to diagnose potential
problems.
Daily Mail 24 Hours Per Day
Nov 25, 2007
Coeliac
CoeliacDisease
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Finger tip whole blood assay for coeliac disease,
a new rapid point of care test
Mäki M, Korponay-Szabo I. Methods and means for detecting gluteninduced diseases 2001, IPN WO02/086509 A19
Korponay-Szabó et al., Coeliac disease case finding and diet
monitoring by point-of-care testing.
Aliment Pharmacol Ther, 2005;22:729-37.
Raivio et al., Self transglutaminase-based rapid coeliac disease
antibody detection by a lateral flow method.
Aliment Pharmacol Ther 2006;24:147-54.
Sensitivity and specificity = EMA, tTG-ab
Coeliac
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Principle of self TG-based rapid
antibody detection
TG
Haemolysis
TG
TG
Label
(antianti- IgA)
IgA)
TG
Formation of
self- TG/anti- TG
complexes
+
Capture to
solid surface
TEST RESULT (5 min)
Coeliac
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Group
-
Alliance apoteket, Norge
Apoteksbolaget, Sverige
Coeliac
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Group
Biocard Celiac Test
- Rapid whole blood tests for coeliac disease,
on site testing from finger tip capillary blood
- Sensitive and specific test (=EMA, TG2-ab) to detect untreated
even clinically silent coeliac disease, meant for case finding,
screening of risk groups and population-based screenings
- No recombinant / purified TG2 antigen is needed
- Used in doctors’offices
No need for laboratory, the test is performed on site, no
laboratory equipment needed, result available in 1-5 minutes.
- CE-marked for home testing, available in pharmacies
- Use at home: Screening of family members, treatment follow
up, “might I have coeliac disease?”
- Indications same as for EMA and tTG-ab, biopsy is so far needed for
final diagnosis
- Immediate availability of results may help physicians to speed
up the diagnostic process and to evaluate dietary
compliance
Coeliac
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Morphology of normal and coeliac disease
affected small bowel mucosa
Coeliac
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Predictors for forthcoming CD
”Mild enteropathy coeliac disease”
Coeliac
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Sens
%
Spesif
%
Mucosal IgAdeposits
93
93
Serum
autoantibodies
76
83
Mucosal villous tip
IELs
88
71
Mucosal γδ IELs
76
60
Mucosal IELs
(Marsh 1)
59
57
HLA DQ2 or DQ8
100
66
Salmi et al., Aliment Pharmacol Ther, 2006
Coeliac disease beyond villous atrophy
Kaukinen et al., Gut 2007
Heavily underdiagnosed worldwide, diagnostic delay
North America, South America,
Europe, Arabic states
India, others
(not in Japanese, black Africans)
The Coeliac Disease Iceberg
Treatment available, but how to
find, diagnose, and treat
Cost benefit issues
Clinical
coeliac disease
Silent
coeliac disease
Manifest
mucosal
lesion
DR3-DQ2,
DR5/7-DQ2
DR4-DQ8
Coeliac disease latency
Normal
mucosal
Healthy individuals morphology
Jejunal morphology
Tools available for screening
and rapid diagnosis
Genetic susceptibility
Finland 1:50
UK 1:100
Many countries 1:100 –1:200
Life-long gluten-free diet
novel therapies
Coeliac
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Mäki M. & Collin P. Lancet 1997;349:1755-59
Celiakipiller på kommande,
forskning och kliniska studier på
gång
Normal slemhinna
Glutenframkallad slemhinnaskada
GLUTEN
HINDRAR LÄKEMEDLET SLEMHINNASKADAN?
The sooner we are ready to meet the future,
the longer we are able to stay there (Ralph Gothoni 1998)
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