Genes comunes en infecciones y enfermedades autoinmunes

Genes comunes en infecciones y
enfermedades autoinmunes
Javier Martín
Autoimmune Diseases: complex aetiology
Rioux & Abbas, Nature , 2005
The Genetic Theory of Infectious Diseases
Contribution of human genetic factors in host-pathogen interactions
C-C Chemokine receptor type 5
CCR5
AIDS
Contribution of human genetic factors in host-pathogen interactions
Duffy antigen/chemokine receptor
DARC
malaria
Contribution of human genetic factors in host-pathogen interactions
Handel & Horuk, Trend Parasitol, 2010
Genome Wide Association studies –GWAs•
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Description of the Human Genome
Advances in genotyping technologies
Reduction in genotyping costs
HapMap project
Genome-Wide Association Studies
(GWAS)
Altshuler & Daly & Lander; Science, 2008
Strategy for GWA studies
Strategy for GWA studies
• Case/control studies. Replication phase. P values < 10-8
• Genetic markers across the whole genome (from 300.000 to 2.5 million SNPs).
• Common variants > 5%
• Non-hypothesis-driven analysis.
• Hypothesis generating approach.
GWAS in Infectious Diseases
De Bakker & Telenti, Nat Genet, 2010
GWAS in Infectious Diseases
GWAS in Infectious Diseases
Khor & Hibberd, Trend Genet, 2012
GWAS in Infectious Diseases: The MHC region
Khor & Hibberd, Trend Genet, 2012
GWAS in Leprosy
HLA
Zhang et al, NEJM, 2009
GWAS in Malaria
Jallow M et al., Nat Genet, 2009
GWAS in Leishmaniasis
HLA in Autoimmune Diseases
HLA association
DQA1*02:
Celiac disease
DRB1*04:
DRB1*03:
DRB1*15:
DRB1* 11:
RA
T1D, SLE
MS, SLE
SSc
B*27: Ankylosing spondylitis
Cw6: psoriasis.
GWAS in Autoimmune Diseases
Lupus
Scleroderma
MHC in Infectious & Autoimmune Diseases
Infectious Diseases
Autoimmune Diseases
Malaria
-B*53
RA
-DRB1*04
Tuberculosis
HLA
SLE
-DRB1*03
Leprosy
- DRB1**15
MS
-DRB1*15
AIDS
- B*57 / -B*27
AS
- B*27
HCV
MICA, -DQB1*03 T1D
HBV
-DR, -DP
CeD
- DQ2/DQ8
Dengue
MICA, MICB
IBD
- DRB*1
- DQB1*03
MHC in Infectious & Autoimmune Diseases
Overlap of leprosy genes with other diseases
Inflammatory Bowel Diseases
Psoriasis -blue Parkinson –red-
Abel & Alcais & Schurr, Curr Opin Immunol, 2014
The host-pathogen interface for leprosy and Crohn’s disease
Khor & Hibberd, Trend Genet, 2012
Common genes in Infection and Autoimmunity
Common genes in Infection and Autoimmunity
Common genes in Infection and Autoimmunity
Better understanding
disease pathogenesis
Prognosis /
biomarkers
Personalized or
Stratified Medicine
New therapeutic targets
Las estudios amplios del genoma –GWAS- han sido muy fructíferos a la hora de
identificar genes asociados a enfermedades autoinmunes y en menor grado a
enfermedades infecciosas.
Existe una genética compartida entre ambos tipos de patología , aunque queda
aún mucho por entender como funciona.
La realización de análisis conjuntos de los GWAS de enfermedades infecciosas y
autoinmune podrían arrojar nuevos datos acerca de la genética compartida
entre este tipo de patologías.
Sería muy útil incorporar datos del genoma de los patógenos a estos estudios
genómicos en humanos.
Aunque el objetivo primario de los estudio genómicos es mejorar el
conocimiento de los mecanismos patogénicos, no hay duda que los avances en
esta área se podrán traducir en mejoras para los pacientes.
Common genes in Infection and Autoimmunity
Lee et al., Science , 2014