CIR studies coeliac disease to understand the interplay between genetic and environmental factors in chronic inflammatory disorders.
Gluten, genes and auto-antibodies
Individuals with coeliac disease get sick when they eat bread or other gluten-containing food. Why?
Coeliac disease patients show strong association with particular gene variants within the human leukocyte antigen (HLA) complex, particularly HLA-DQ2 and HLA-DQ8. These HLA molecules are directly involved in the pathogenesis of coeliac disease by binding and presenting gluten peptides to disease-specific T cells in the intestines of coeliac patients.
Presence of IgA and IgG antibodies specific for the auto-antigen transglutaminase (TG)2 is an other hallmark of active coeliac disease. Conspicuously, TG2 is not only the target for auto-antibodies in coeliac disease, but it is also important for creation of antigenic gluten T-cell epitopes.
Currently scientists at CIR are trying to understand how disease specific auto-antibodies to TG2 are generated, and why auto-antibody production is dependent on HLA-DQ2 expression as well as dietary gluten exposure.