Abstract

Celiac disease (CD) is a genetically predisposed, T cell-mediated and autoimmune-like disorder caused by dietary exposure to the storage proteins of wheat and related cereals. A gluten-free diet (GFD) is the only treatment available for CD. The celiac immune response mediated by CD4+ T-cells can be assessed with a short-term oral gluten challenge. This study aimed to determine whether the consumption of bread made using flour from a low-gluten RNAi wheat line (named E82) can activate the immune response in DQ2.5-positive patients with CD after a blind crossover challenge. The experimental protocol included assessing IFN-γ production by peripheral blood mononuclear cells (PBMCs), evaluating gastrointestinal symptoms, and measuring gluten immunogenic peptides (GIP) in stool samples. The response of PBMCs was not significant to gliadin and the 33-mer peptide after E82 bread consumption. In contrast, PBMCs reacted significantly to Standard bread. This lack of immune response is correlated with the fact that, after E82 bread consumption, stool samples from patients with CD showed very low levels of GIP, and the symptoms were comparable to those of the GFD. This pilot study provides evidence that bread from RNAi E82 flour does not elicit an immune response after a short-term oral challenge and could help manage GFD in patients with CD.

Highlights

  • Celiac disease (CD) is an autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals

  • Many CD-related epitopes are recognized by CD4+ T cells [4], a 33-mer peptide derived from α-gliadin, which contains six copies of three overlapping human leukocyte antigen (HLA) DQ2.5-restricted T cell epitopes, is the main contributor to the immunogenicity of gluten [5]

  • One patient was excluded from the study because of consumption of gluten-containing foods, and the data were removed from the analysis

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Summary

Introduction

Celiac disease (CD) is an autoimmune enteropathy caused by exposure to dietary gluten in genetically predisposed individuals. Production of interferon (IFN-γ) by relevant T cells can be evaluated in peripheral blood by the enzyme-linked immunospot (ELISPOT) assay after a short-term (3 days) oral gluten challenge [6]. This approach has many applications to identify CD dominant epitopes, to uncover differences in the immune response between different cereals, and for testing new therapies for CD [7,8,9]

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