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Immunoregulated insulitis and slow-progressing type 1 diabetes after duodenopancreatectomy

Abstract : Aims/hypothesis: We report the case of a woman who underwent a partial pancreatectomy for a serous cystadenoma when aged 56 years. She had been diagnosed with diabetes 6 years before and had Hashimoto's thyroiditis. Despite positive anti-GAD autoantibodies (GADA) and previous surgery, she was transiently weaned off long-acting insulin. Blood glucose levels remained well controlled with low-dose long-acting insulin. Insulin needs eventually increased 8 years after surgery, in conjunction with anti-zinc transporter 8 (ZnT8) seroconversion and decreasing residual C-peptide. We hypothesised that the surgical pancreas specimens and blood autoimmune T cell responses may provide correlates of this indolent clinical course. Methods: Beta and alpha cell area and insulitis were quantified on pancreas head tissue sections obtained at surgery. Blood T cell responses against beta cell antigens were analysed by enzyme-linked immunospot. Results: Pancreas sections displayed reduced beta cell and normal alpha cell area (0.27% and 0.85% of section area, respectively). High-grade insulitis was observed, mostly in insulin-containing islets, with a peri-insulitis pattern enriched in T cells positive for regulatory forkhead box protein 3 (FOXP3). In vitro challenge with beta cell antigens of circulating T cells collected 4 and 9 years after surgery revealed dominant and persistent IL-10 responses; IFN-γ responses increasing at 9 years, after anti-ZnT8 seroconversion, was observed. Conclusions/interpretation: Despite persistent GADA and the histopathological finding of insulitis and decreased beta cell area 6 years after diabetes diagnosis, glycaemic control was maintained with low-dose insulin up to 8 years after surgery. Regulated T cell responses towards beta cell antigens and FOXP3-positive peri-insulitis suggest spontaneous long-term regulation of islet autoimmunity after substantial beta cell loss, and eventual autoimmune progression upon anti-ZnT8 seroconversion.
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Contributor : Roberto Mallone Connect in order to contact the contributor
Submitted on : Sunday, October 17, 2021 - 2:42:11 AM
Last modification on : Thursday, April 7, 2022 - 1:58:20 PM
Long-term archiving on: : Tuesday, January 18, 2022 - 6:06:21 PM


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Pauline Faucher, Frédéric Beuvon, Daniela Fignani, Guido Sebastiani, Georgia Afonso, et al.. Immunoregulated insulitis and slow-progressing type 1 diabetes after duodenopancreatectomy. Diabetologia, Springer Verlag, 2021, Online ahead of print. ⟨10.1007/s00125-021-05563-8⟩. ⟨inserm-03381517⟩



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