Local challenge on oral mucose with an alpha-gliadin related synthetic peptide in patients with celiac disease

OBJECTIVE: Gluten-derived peptides (e.g., amino-acids 31-49 of alpha-gliadi n) have been shown to cause changes typical of celiac disease in the gut. G luten-derived peptides have mostly been used in in vitro studies. The easie st access to the gastrointestinal system may be the mouth. in the present s tudy we were interested to see whether a synthetic peptide corresponding to amino-acids 31-49 of alpha-gliadin could induce inflammatory changes in th e oral mucosa after a local challenge in celiac disease patients. METHODS: The challenge was made by injecting the peptide solution at a conc entration of 10 mu g/ml submucosally into the oral mucosa of 10 celiac dise ase patients after a gluten-free diet (GFD) and 12 healthy control subjects . B and CD45RO+ T cells, mast cells, CD3+, CD4+, CD8+ lymphocytes, and alph a beta and gamma delta T-cell receptor-bearing (TcR alpha beta, TcR gamma d elta) lymphocytes were counted and HLA DR expression was determined. The ex pression of CD25 and Ki-67 antigen was also examined. RESULTS: The peptide significantly increased the total number of T cells in the lamina propria of the celiac disease patients. The expression of T-cel l activation marker CD25 (IL-2 receptor), but not that of cell proliferatio n marker Ki-67, was also significantly increased in the lamina propria afte r peptide challenge. Such a reaction was not observed in the controls. The numbers of CD3+ and CD4+ T cells in the lamina propria were also increased in celiac disease patients after the challenge. The count of TcR gamma delt a+ cells was very small in the oral mucosa in celiac disease and showed no increase when the oral mucosa was challenged with the peptide. The expressi on of HLA DR staining was enhanced after the submucosal peptide challenge i n celiac disease; however, the difference was not statistically significant . CONCLUSIONS: The results show that in the celiac disease patients after the peptide challenge the oral mucosal lamina propria responds with a nonproli ferative increase of lymphocytes. Thus, submucosal challenge with the pepti de 31-49 can be used as an aid in the diagnosis of celiac disease. However, further studies with optimized methodology, including various concentratio ns of the peptide, adjuvants, other peptides, etc., are warranted, especial ly because the oral mucosa provides the easiest access to an in vivo peptid e challenge in celiac disease. (Am J Gastroenterol 2000;95:2880-2887. (C) 2 000 by Am. Coll. of Gastroenterolgy).