Immunoregulated insulitis and slow-progressing type 1 diabetes after duodenopancreatectomy.
Autoimmunity
Duodenopancreatectomy
Insulin secretion
Regulatory T cells
Type 1 diabetes
Journal
Diabetologia
ISSN: 1432-0428
Titre abrégé: Diabetologia
Pays: Germany
ID NLM: 0006777
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
10
04
2021
accepted:
06
07
2021
pubmed:
16
9
2021
medline:
1
4
2022
entrez:
15
9
2021
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 34522983
doi: 10.1007/s00125-021-05563-8
pii: 10.1007/s00125-021-05563-8
doi:
Substances chimiques
Autoantibodies
0
Insulin
0
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2731-2740Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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