EVIDENCE THAT GLUTEN SENSITIVITY IS AN IMMUNOLOGICAL DISEASE

This review highlights recent publications on the subject of gluten se nsitivity. The term gluten sensitivity should supersede celiac disease because it embraces all individuals of appropriate genetic background whose T cells are sensitized to gluten protein, including all dermati tis herpetiformis cases with immunoglobulin A+ skin biopsy results, sy mptomatic celiac disease patients, and the larger majority with latent (or subclinical) disease. Such individuals are predisposed to intesti nal mucosal damage by a remarkably tight association (>95%) with the D Qw2 specificity. A spectrum of mucosal lesions (besides the ''flat'' l esion) occurs with gluten sensitivity; the milder lesions have yet to be recognized by many physicians and pathologists as caused by gluten in particular and to presumptive T-cell activity in general. That thes e are all T-cell-mediated lesions is suggested by their similarity to defined immunologic models of enteropathy that have been pursued in ex perimental animals. The response of rectal mucosa is best explained by the recruitment of sensitized T cells to gluten deposition. Although gammadelta cells have excited much interest throughout the immunologic community of late, their role in gluten-induced mucosal pathology is far from clear. It should also be noted that the tempo of their mucosa l appearance and disappearance is much slower than that of CD8 alphabe ta lymphocytes. Antibodies to alpha-gliadin remain useful for predicti ng, and screening for, gluten sensitivity. There is clearly little dou bt that gluten sensitivity is an immunologically determined disease an d work reviewed herein considerably strengthens that view. Nevertheles s, it is hoped that future work with cloned T cells will provide the f inal, but necessary, piece of evidence that will confirm the view that gluten sensitivity is primarily an immunologically driven condition.