title: Integration of genetic and immunological insights into a model of celiac disease pathogenesis.
abstract: Celiac disease (CD) is a gluten-sensitive enteropathy that develops in genetically susceptible individuals by exposure to cereal gluten proteins. This review integrates insights from immunological studies with results of recent genetic genome-wide association studies into a disease model. Genetic data, among others, suggest that viral infections are implicated and that natural killer effector pathways are important in the pathogenesis of CD, but most prominently these data converge with existing immunological findings that CD is primarily a T cell-mediated immune disorder in which CD4(+) T cells that recognize gluten peptides in the context of major histocompatibility class II molecules play a central role. Comparison of genetic pathways as well as genetic susceptibility loci between CD and other autoimmune and inflammatory disorders reveals that CD bears stronger resemblance to T cell-mediated organ-specific autoimmune than to inflammatory diseases. Finally, we present evidence suggesting that the high prevalence of CD in modern societies may be the by-product of past selection for increased immune responses to combat infections in populations in which agriculture and cereals were introduced early on in the post-Neolithic period.
authors.affiliation: Department of Medicine, University of Chicago, Illinois 60637, USA.
authors.forename: Valérie
authors.initials: V
authors.lastname: Abadie
authors.forename: Ludvig M
authors.initials: LM
authors.lastname: Sollid
authors.forename: Luis B
authors.initials: LB
authors.lastname: Barreiro
authors.forename: Bana
authors.initials: B
authors.lastname: Jabri
mesh_terms: D000818:Animals; D002446:Celiac Disease / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D020022:Genetic Predisposition to Disease; D005983:Glutens / Q000276:immunology; D006801:Humans; D012307:Risk Factors
chemical_list: D005983:Glutens