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home - Small Bowel - Coeliac Disease - Coeliac Pathogenesis Written by Dr Sebastian Zeki

Coeliac Pathogenesis

Coeliac disease aetiology theories: Genetic (10-15% have first degree relative with it). Viral - adenovirus type 12 more common in coeliac. Alpha gliadin has amino acid homologous to the 54KDa E1b protein coat of adenovirus 12 so molecular mimicry is implicated. Breakdowningut TTG secreted by fibroblasts and inflammatory cells in lamina propria TTG Glutamine containing peptides Glutamic acid Deamidation Because it is negatively charged it can bind to HLA DQ2Pro-inflammatory T cell activation + G l u t e n GluteninGliadin Wheat Rye Barley Hordein Secalin Secalin, gliadin, avenin and hordein are collectively called prolamins (soluble in ethanol) and have similar amino acid residues. Avenin is less toxic and oats may be safe Oats Avenin Specific peptide motifs as yet not specifically isolated Cellular immunity Humoral immunity The role of antibodies in disease pathogenesisAntigliadin antibodies are not essential for the pathogenesis of coeliac disease.IgA endomysial antibodies are rarely found without coeliac- however CD patients without dont differ to those with the antibodies.Antibodies against TT may be of some pathogenic importance.CD patients also have serum antibodies against other food proteins such as beta-lactoglobulin, casein, and ovalbumin- reason unclear. Genetic factors:It is associated withHLA-DQ2 and/or DQ8 gene locus.- HLA contribution to the development of celiac disease among siblings is 36 %.Homozygosity for HLA DQ2 has been associated with an increased risk for refractory coeliac disease and enteropathy-associated T-cell lymphoma .It is associated with chromosome 15q26, which contains a type I diabetes susceptibility locus.It is associated with chromosome 5q and possibly 11q.It is associated with an unidentified gene on chromosome 6p.There is a weak link with variants of the myosin IXB gene (MYO9B) located on chromosome 19 which hasbeen associated with impaired intestinal barrier function and linked to coeliac disease, refractory celiac disease and enteropathy associated T-cell lymphoma . EpidemiologyIt occurs primarily in whites of northern European ancestry.Punjabis and Gujaratis from India who lived in England developed this disorder 2.7 times as frequently as Europeans when on a gluten-rich diet.The prevalence of CD is around 1:184 In the at-risk groups, the prevalence is 1:22 in 1st-degree relatives and 1:39 in 2nd-degree relatives. Pathogenesis of Coeliac Disease Endosperm Embryo Bran Written by Dr Sebastian Zeki

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