The immunologic basis for celiac disease and related disorders

Celiac disease is the classical food-sensitive enteropathy and is caused by an antigen-specific immunologic hypersensitivity response to gluten within the small intestinal mucosa. Antibody and T-cell hypersensitivity may play a role in vivo, but it is more likely that the primary problem is an inappropriate T-cell response to gluten. The deleterious effects of gluten in celiac patients can be completely explained by the immune-mediated alterations in upper small-intestinal mucosal shape; these alterations include the replacement of long villi and short crypts with short or absent villi and hyperplastic crypts. It is an extremely unusual disease in that it is highly linked to human leukocyte antigen (HLA)-DQ2, and CD4+ T-cell clones that recognize gluten in the context of DQ2 have been isolated from celiac mucosa lamina propria. HLA-DQ2 is commonly used in Whites, but the incidence of celiac disease varies greatly between different countries and with time, without any obvious explanation. Celiac disease is also unusual in that it has features of autoimmune disease. Patients with active disease have immunoglobulin (Ig)A antibodies in endomysium, an uncharacterized extracellular matrix protein, and the presence of these antibodies is very specific for this condition. However, because celiac disease is more common in IgA-deficient patients, the IgA antiendomysial antibodies are unlikely to be pathogenic.