coeliac disease mechanisms

The relationship of coeliac disease to gluten intolerance is accepted, but the mechanism is still incompletely understood
Coeliac disease onset
Certain genetic variants of the major histocom-patibility complex (MHC) proteins are linked to increased susceptibility to autoimmune diseases. Hovhannisyanin Nature propose a mechanism that accounts in part for one such association, the onset of coeliac disease, which is tightly associ¬ated with the expression of human HLA-DQ8 and the mouse equivalent, IAg7. This new work shows that the structural properties associated with the lack of an Asp57 found in all other MHC alleles alters the specificity of HLA-DQ8 and IAg7. This leads to transaminase-mediated deamination of glutamine residues in dietary gluten peptides, causing them to bind more tightly to disease-associated MHC alleles and to mount an amplified anti-gluten response. HI..A-DQ8 and IAg7 are also closely linked to type 1 diabetes, though it is not clear whether a similar mechanism is involved.
Hovhannisyan et al 2008 The role of HLA-DQ8 β57 polymorphism in the anti-gluten T-cell response in coeliac Nature vol 456 545-548

Martin Eastwood
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