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T-cell mediated immunity to gliadin is elicited in the gut mucosa of type 1 diabetes patients only in presence of celiac disease comorbidity

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posted on 2025-06-24, 17:25 authored by Carmen Gianfrani, Alessandra Camarca, Stefania Picascia, Serena Vitale, Ilaria Mottola, Martina Carpinelli, Mariantonia Maglio, Silvia Gregori, Adriana Franzese, Renata Auricchio, Riccardo Troncone

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 subjects were enrolled (median age 10 years) and divided in 5 groups based on T1D and/or CeD diagnosis. All patients underwent the upper endoscopy for suspicion of CeD or gastrointestinal complaints, and duodenal biopsies 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 subjects negative for CeD, also in the presence of antibodies neutralizing regulatory cytokines IL10 and TGF-b. 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 subjects in absence of CeD comorbidity.

Funding

This work was supported by the Italian Ministry of Health for the research grant RF-2016-02361372 to CG and SG, and by Italian Society for the Celiac Disease–AIC, for the fellowship to SV (PROJECT 009_FC_2016).

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