THE MAJORITY OF RELATIVES OF CELIAC PATIENTS WITH POSITIVE RECTAL GLUTEN CHALLENGE HAVE A LOW GRADE SMALL INTESTINAL ENTEROPATHY

Abstract

111 A significant infiltration of CD3 and γδ+ lymphocytes is induced in the rectal mucosa of coeliac patients by a gliadin enema. Interestingly, a subset of siblings of coeliac children also react to rectal instillation of gliadin. Aim of this study has been to correlate in coeliac relatives the results of the rectal gluten challenge with the immunohistochemical features of the small intestinal mucosa, particularly with density of cells infiltrating the epithelium and signs of activated T cell mediated immunity. In 16 treated coeliac children, 10 disease-controls and 30 siblings of coeliacs, rectal biopsies were obtained before and 6 hours after rectal challenge with a peptic-tryptic digest of gliadin (Gastroenterology 1996; 111: 318-24 ). CD3+ and γδ+ lymphocytes were counted and a discriminant score was calculated. Jejunal biopsies were obtained 13 siblings and cryostat sections were incubated with antiCD3, antiTCRγδ, antiCD25 (IL2 receptor), antiCD54 (ICAM1) antibodies, and processed by immunohistochemistry (PAP or APAAP techniques). After local instillation of gliadin, in coeliac patients, but not in controls, immunohistochemistry showed a significant increase in CD3+ and γδ+ cells. The discriminant analysis allowed correct classification of 100% coeliacs and controls, while 11/30 (37%) siblings were classified as coeliacs. All of them had a negative serology (AGA, EMA) and a normal architecture of the jejunal mucosa. Nevertheless, the immunohistochemical analysis of the jejunal biopsies showed in 5/6 siblings with a positive response to rectal gluten challenge, but only in 1/7 of those with a negative response, increased density of CD3+ and/or γδ+ lymphocytes. In no case increased number of CD25+ cells or enhanced expression of ICAM 1 was observed. Our results demonstrate that in siblings of coeliac patients the positivity to rectal gluten challenge is often accompanied in the small intestine by a low-grade enteropathy characterized by a lymphocyte infiltration of the epithelium. The rectal gluten challenge is proposed as a useful tool to detect an abnormal mucosal immune response to gluten.