PROLIFERATION-ASSOCIATED MARKERS IN THE CELIAC DUODENUM

Objective: The aim of this study was to define the degree of enterocyte proliferation in the duodenum of patients with both treated and untreated coeliac disease, using bromodeoxyuridine incorporation. Second, we wished to determine whether surface duodenal enterocytes expressed markers associated with cellular proliferation and/or altered differentiation. Design: We examined bromodeoxyuridine incorporation in duodenal biopsy specimens obtained per-endoscopically from seven untreated and six treated coeliac patients and from 18 normal controls. In addition, we examined the expression of the transferrin receptor (TfR) and two novel proliferation-associated antigens, M21C5 and M2B3, which recognize antigens expressed on colonic tumour cells. Results: Both treated and untreated patients were found to have a significantly increased proportion of enterocytes in S phase. The expression of the TfR was limited to the crypts and lower portion of the villus in normal controls; TfR was detected on surface enterocytes in coeliac duodenum. Expression of the 142 kDa proliferation-associated antigen M2B3 was markedly increased on both crypt and surface enterocytes in the coeliac duodenum. This antigen was present faintly, if at all, in normal crypts. M21C5 was not detected in either normal or coeliac duodenal epithelial cells. Conclusion: These data highlight the hyperproliferative state of coeliac duodenal enterocytes. In addition to increased crypt cell indices, surface enterocytes express antigens normally associated with proliferation.