3 The immunology of coeliac disease

Abstract

Coeliac disease is defined as that disorder in which there is an abnormality of the small intestinal mucosa manifested by contact with the gluten of wheat and certain other cereal grains. In the immunological theory of the pathogenesis of coeliac disease, gluten, or a component, is viewed as the antigen responsible for the immune response. The search for the gluten component responsible for ‘toxicity’ and, by implication, antigenicity, is described. The antigen may be presented differently to the immune system by an abnormal cell membrane, either of the enterocyte, lymphocyte or macrophage. Alternatively, increased amounts of antigen may be absorbed due to increased membrane binding or permeability, either of which could be genetically determined. As a further possibility, coeliac disease may occur because the patients are immunologically hyperresponsive and this too appears to be genetically determined. The perturbations which occur in the mucosal immune system and the systemic immune system are described. It is conceivable that the major complications described (intestinal ulceration, malignancy and splenic atrophy) result from immunological disturbances. The incidence of childhood coeliac disease is declining, which may be due to altered exposure to, or increased protection from, the antigen in infancy, or to changes in environmental factors. The immunological mystery of coeliac disease continues to excite interest and fascination, and has certainly been a stimulus to our deeper understanding of gastrointestinal immunology.