Coeliac disease: An analysis of aetiological possibilities and re-evaluation of the enzymopathic hypothesis

Abstract Although it is well established that components of wheat gluten and structurally-related cereal proteins produce intestinal damage in Coeliac disease (CD), the primary defect which confers upon the host susceptibility to these dietary substances remains a mystery. To date, three main hypotheses have been framed to explain this susceptibility, but none has yet been proven. Diagrammatic representation of these aetiologic hypotheses facilitates their analysis and illustrates the potential importance of a relatively ignored possibility, i.e., that there may be a defect in the intraluminal phase of the in vivo processing of dietary gluten. We suggest that future work should be directed towards investigating the potential role of abnormalities of this phase in the aetiology of CD.