Coeliac disease: genetic, immunological and environmental factors in disease pathogenesis

Coeliac disease in humans is activated by the dietary ingestion of wheat gliadins and similar proteins in other grains. We have studied genetic, immunological and environmental factors that may play a role in the pathogenesis of disease. In mice, two genetic regions, the major histocompatibility complex (H-2) and the immunoglobulin heavy chain constant region, were shown to regulate the production of anti-gliadin antibody. In coeliac disease patients on a gluten-free diet, elevated levels of antigliadin antibody were associated with the immunoglobulin heavy chain allotype marker G2m(n). Studies of additional environmental factors involved in coeliac disease revealed a region of amino acid sequence homology and immunological crossreactivity between A-gliadin, a wheat gliadin component known to activate coeliac disease and the Elb early region protein of human adenovirus 12, an adenovirus serotype usually isolated from the human intestinal tract. Specific HLA markers may be associated with coeliac disease because they reflect the host's response to virus.