T-Cell Mediated Immunity to Gliadin Is Elicited in the Gut Mucosa of Type 1 Diabetes Patients Only in Presence of Celiac Disease Comorbidity

Abstract

Type 1 diabetes (T1D) and celiac disease (CeD) are two strongly associated autoimmune disorders, as they share genetic risk factors and immunopathogenic mechanisms. Several studies suggest an implication of gluten proteins, the causative antigen of CeD, in T1D pathogenesis. We investigated whether a gliadin-specific T-cell reactivity is present in the gut mucosa of children with T1D, with or without CeD comorbidity. Thirty-three young children were enrolled (median age 10 years) and divided in five groups based on T1D and/or CeD diagnosis. All patients underwent upper endoscopy for suspicion of CeD or gastrointestinal complaints, and duodenal biopsy specimens were processed for analysis of lymphoid cells phenotype and T cell–mediated reactiveness to gliadin. No substantial differences were found in the percentages of various T-cell subsets between the groups. No gliadin T-cell reactivity was found in T1D children negative for CeD, also in the presence of antibodies neutralizing regulatory cytokines interleukin 10 and transforming growth factor β. By contrast, a marked T-cell response to gliadin was detected in T1D with either potential (positive for CeD-associated autoantibodies and normal mucosa histology) or full-blown CeD (villous atrophy). In conclusion, no adaptive immunity to gluten occurs in the small intestine of T1D children in the absence of CeD comorbidity. Article Highlights It has been hypothesized that dietary proteins act as environmental factors in type 1 diabetes pathogenesis. This study investigated whether gliadin-specific T cells are present in the small intestine of children with type 1 diabetes, without or with celiac disease comorbidity. No sign of gliadin-reactive T cells, either proinflammatory or regulatory, was observed in the gut mucosa of children with type 1 diabetes negative for celiac disease autoimmunity. Interferon-γ producing T cells were detected in gut mucosa biopsy specimens of children with diabetes seropositive for antitissue transglutaminase antibodies. Our study does not support a pathogenic role of intestinal T cell–mediated immunity to gluten in type 1 diabetes pathogenesis.