4.7 Article

Immunoregulated insulitis and slow-progressing type 1 diabetes after duodenopancreatectomy

期刊

DIABETOLOGIA
卷 64, 期 12, 页码 2731-2740

出版社

SPRINGER
DOI: 10.1007/s00125-021-05563-8

关键词

Autoimmunity; Duodenopancreatectomy; Insulin secretion; Regulatory T cells; Type 1 diabetes

资金

  1. JDRF [2-SRA-2016-164-Q-R]
  2. Fondation pour la Recherche Medicale [EQU20193007831]
  3. Agence Nationale de la Recherche [ANR-19-CE15-0014-01]
  4. Innovative Medicines Initiative 2 Joint Undertaking from the EU Horizon 2020 programme [115797, 945268]
  5. European Federation of Pharmaceutical Industries and Associations
  6. Leona M. & Harry B. Helmsley Charitable Trust
  7. JDRF Postdoctoral Fellowship [3-PDF-2020-942-A-N]
  8. JDRF

向作者/读者索取更多资源

Despite persistent GADA and histopathological insulitis findings with decreased beta cell area 6 years after diabetes diagnosis, this case study shows that good glycemic control was maintained with low-dose insulin for up to 8 years post-surgery. Regulated T cell responses to beta cell antigens and FOXP3-positive peri-insulitis suggest long-term spontaneous regulation of islet autoimmunity after significant beta cell loss, with eventual autoimmune progression upon anti-ZnT8 seroconversion.
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-gamma 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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