GLUTEN SENSITIVITY IN THE RECTAL MUCOSA OF FIRST-DEGREE RELATIVES OF CELIAC-DISEASE PATIENTS

Background/Aims: Rectal gluten challenge is a simple, sensitive, and s pecific test of mucosal gluten sensitivity. Our aims in this study wer e to evaluate gluten sensitivity in a group of relatives of celiac pat ients and to compare these findings with those obtained on small bowel histology, celiac disease-related serology, and HLA typing. Methods: A 4-h rectal gluten challenge was performed with 6 g of crude gluten i n saline solution in 29 first-degree relatives, 20 well-diagnosed celi ac patients, and 10 subjects in whom celiac disease had been excluded. The number of intraepithelial lymphocytes in pre- and postchallenge f rozen rectal biopsies (pan T-cell immunocytochemistry) was quantified by computerized image analysis. Results: The intraepithelial lymphocyt e response after gluten instillation was significantly higher in celia c disease patients (median, 126% increase above the baseline count; 95 % confidence interval: 61-213%) compared with control subjects (median , -5%; 95% confidence interval: -29-5%). Using a cut-off of 20% change in intraepithelial lymphocyte count, 14 relatives (48%) showed a celi ac-like response. Two of these subjects had partial villous atrophy an d increased lymphocyte counts in the small bowel mucosa. One of them a lso exhibited a positive celiac disease-related serology and the typic al celiac human lymphocyte antibody (HLA) DQ2. The remaining 12, and a ll those relatives with a negative challenge, had normal small bowel m ucosa and were negative for antigliadin and endomysial antibodies. The characteristic celiac HLA (DQA1 0501 DQB1 0201 heterodimer) was ident ified in five relatives with positive challenge (including the patient with more severe mucosal atrophy) but was also present in eight relat ives with no evidence of gluten sensitivity in the rectal mucosa. Conc lusions: Our study characterizes a subgroup of relatives of celiac pat ients who show mucosal evidence of sensitization after local instillat ion of gluten in the rectum but who have no other features of celiac d isease.