Lack of immunogenicity of hydrolyzed wheat flour in coeliac patients upon a short-term oral challenge

Background: Gluten free diet is currently the only reliable therapeutic strategy in coeliac disease (CD) however, for many patients the compliance is still poor. Aim: In the present study, we investigated in coeliac patients the immunogenicity of wheat flour pre-treated with a sourdough made of selected lactobacilli and fungal proteases (hydrolyzed wheat gluten) through the innovative approach of the short-term oral challenge. Methods: The immunogenicity of hydrolyzed wheat gluten was evaluated both in vitro on intestinal T cell lines and in vivo in treated CD patients after a brief oral (3 days) gluten challenge. Twenty treated CD patients were enrolled and randomized into two groups. Patients ate bread prepared with hydrolyzed wheat flour or with natural wheat flour (10gr of gluten/die). INF-? responses were assessed by ELISPOT in peripheral blood before and 6 days after the challenge to both whole untreated gliadin and immunodominant DQ2.5-glia-?1/2 peptides. Results: Hydrolyzed wheat did not activate T lymphocytes from coeliac intestinal mucosa. Consistently with the in vitro results, no significant INF-? secreting T cells reactive to natural gliadin or to the dominant peptides were observed in patients that consumed hydrolyzed wheat flour. By contrast, the consumption of natural wheat gluten mobilized IFN-? secreting cells in blood (p<0.05). Conclusions: We confirm that fermentation of wheat flour with sourdough lactobacilli and fungal proteases is able to abolish the T cell immunogenicity of gluten in coeliac patients. Our data also support the idea that an easy in vivo procedure, such as a short-term oral challenge, can be an useful tool to test the efficacy of novel therapeutic approaches.