Lack of immunogenicity of hydrolysed wheat flour in patients with coeliac disease after a short‐term oral challenge

Abstract

We confirm that fermentation of wheat flour with sourdough lactobacilli and fungal proteases is capable of abolishing the T cell immunogenicity of gluten in coeliac patients. Our data also validate the short-term oral challenge as a useful tool for testing the efficacy of novel therapeutic approaches.

In Celiac Disease Patients the In Vivo Challenge with the Diploid Triticum monococcum Elicits a Reduced Immune Response Compared to Hexaploid Wheat

“…In line with previous studies, [ 28,34 ] we observed a large individual variability in the level of IFN‐γ production among the CD volunteers. A variable number of IFN‐γ SFC was detected in the PBMCs even before the gluten intake started (day 0).…”

“…In order to address this hypothesis, we further analyzed the capability of TM and TA gluten challenge to mobilize T cells reactive to five immune‐dominant epitopes from α‐ , ω‐ , and γ‐gliadins in a subgroup of CD volunteers. Despite a wide individual variability in the profile of recognized peptides, that is compatible with previous studies, [ 28,34,36 ] overall, we observed that the TM challenge elicited a reduced number of epitope specific T cells. In more details, the patients eating TM bread had a lower frequency of IFN‐γ secreting cells reactive to DQ2.5‐glia α1a/b/α2 epitopes, harbored in the known 33‐mer peptide, in contrast to patients eating TA bread.…”

“…This is more likely due to the basal activation of the lymphocytes in these subjects, despite the clinical remission and the gluten‐free diet, as reported in other studies. [ 28,34 ] On the other hand, we cannot exclude that other no‐gluten proteins, in particular those named ATIs, might stimulate an immune response in our CD patients who underwent the wheat challenge. However, recent studies and our unpublished data reported a very lower amount of ATIs in T. monococcum than in T. aestivum .…”

“…Noteworthy, the SGC has been recently applied to assess the efficacy of novel therapeutic strategies for the treatment of CD. [ 28–30 ] In the present study, two cohorts of celiac patients compliant to GFD were monitored for cytokine production by the enzyme‐linked immunospot (EliSpot) assay and by quantitative real‐time PCR, before and after the SGC with TM or TA bread.…”

Inducción de mecanismos de la respuesta innata por péptidos de gliadinas en un modelo de enteropatía experimental

“…En los IELs, se encuentran tres poblaciones mayoritarias de células: linfocitos con TCR α/β + CD8 + , linfocitos con TCR / + y células NK. Aunque solo en el caso de los linfocitos TCR α/β + CD8 + pudo observarse una respuesta específica (Mandile et al 2017;Mazzarella et al 2008). En conjunto, estas células son activadas por IFNs tipo I e IFN, reconocen señales de estrés celular expresadas por los enterocitos y son inductores de apoptosis de enterocitos (Olaussen et al 2002).…”