Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease

Coeliac disease (CD) is caused by a CD4 T helper cell type 1 (Th1) response in the small intestinal mucosa to dietary gluten. As the major Th1 inducin g cytokine, interleukin 12, is undetectable in CD gut mucosa, the mechanism by which Th1 effector cells are generated remains unknown. Interferon (IFN ) alpha, a cytokine capable of promoting IFN-gamma synthesis, has been impl icated in the development of Th1 mediated immune diseases. Here we report a case of CD-like enteropathy in a patient receiving IFN-alpha for chronic m yeloid leukaemia, Morphological assessment of duodenal biopsies taken from the patient showed total villous atrophy, crypt cell. hyperplasia, and a hi gh number of CD3(+) intraepithelial lymphocytes. Both antigliadin antibodie s and antiendomysial antibodies were positive. RNA analysis revealed pronou nced expression of IFN-gamma. Withdrawal of gluten from the diet resulted i n a patchy improvement in intestinal morphology, normalisation of laborator y parameters, and resolution of clinical symptoms. By western blot analysis , IFN-alpha protein was seen in the duodenal mucosa from untreated CD patie nts but not in controls. This was associated with marked expression of IFN- gamma protein in CD mucosa. Collectively, these results suggest a role for IFN-alpha in promoting Th1 responses to gluten.