Gliadin‐reactive T cells in Italian children from preventCD cohort at high risk of celiac disease

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The prevalence of celiac disease (CD) is 1–3% in the general population and 5–15% among first‐degree relatives of patients 1. HLA‐DQ genes predispose to CD, as most patients are HLA‐DQ2 or HLA‐DQ8 positive. However, less than 5% of DQ2/DQ8‐positive individuals in the general population develop the disease, and several other risk genes have been identified 2. HLA molecules are involved in CD pathogenesis as gluten, especially after being deamidated by tissue transglutaminase (tTG), bind to HLA‐DQ2 or HLA‐DQ8 and activate intestinal T lymphocytes, prevalently CD4+ T cells 5.
Celiac disease affects subjects of all ages and clinical presentations differ 8. Young CD patients usually present gastrointestinal symptoms, namely diarrhea, malabsorption, and abdominal pain, while adults often present such extra‐intestinal manifestations as anemia or osteoporosis 8. It is not known whether the differences in the time of disease onset, clinical manifestations, and responsiveness to dietary therapy are consequences of diverse intestinal immunity to gluten. Furthermore, most studies of the gluten‐induced inflammatory cascade were performed in adults, and very little is known about the antigluten immune response in childhood CD 5. Indeed, three immunodominant peptides (DQ2.5‐glia‐α‐1/2, DQ2.5‐glia‐ω‐1/2, and DQ2.5‐glia‐γ‐1) have been found to account for more than 95% of the T‐cell response to gluten in adult celiacs 13. A very recent study demonstrated a profile of immunodominant epitopes in pediatric CD not dissimilar from that found in adults and confirmed that deamidation greatly increases T‐cell responses 17. Besides a strong Th1 response to gluten, which mediates mucosal damage 18, anti‐inflammatory T cells have been described in CD gut mucosa 20. Such regulatory T cells may be involved in promoting CD remission after a gluten‐free diet and in preventing progression to mucosal damage.
Prevent Celiac Disease (http://www.preventcd.com) is an international project sponsored by the European Union's sixth Framework Programme. Children enrolled in the study had at least one‐first‐degree relative affected by CD, were HLA‐DQ2 and/or HLA‐DQ8 positive, and were followed for CD development since the age of 4 months 24. During follow‐up, children with CD serological markers and/or persistent symptoms underwent duodenal biopsy. The biopsies obtained gave us the opportunity to investigate the specific intestinal reactivity to the causative antigen, the effect of tTG modification on gluten antigenicity, and the possible role of immune regulatory pathways in controlling the adverse T‐cell response in a very early phase of CD development.

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