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01-08-2021 | Insulins | Original Article

Insulitis in the pancreas of non-diabetic organ donors under age 25 years with multiple circulating autoantibodies against islet cell antigens

Authors: Silke Smeets, Diedert Luc De Paep, Geert Stangé, Katrijn Verhaeghen, Bart Van der Auwera, Bart Keymeulen, Ilse Weets, Zhidong Ling, Peter in’t Veld, Frans Gorus

Published in: Virchows Archiv | Issue 2/2021

Abstract

Autoantibodies against islet cell antigens are routinely used to identify subjects at increased risk of symptomatic type 1 diabetes, but their relation to the intra-islet pathogenetic process that leads to positivity for these markers is poorly understood. We screened 556 non-diabetic organ donors (3 months to 24 years) for five different autoantibodies and found positivity in 27 subjects, 25 single- and two double autoantibody-positive donors. Histopathological screening of pancreatic tissue samples showed lesion characteristic for recent-onset type 1 diabetes in the two organ donors with a high-risk profile, due to their positivity for multiple autoantibodies and HLA-inferred risk. Inflammatory infiltrates (insulitis) were found in a small fraction of islets (<5%) and consisted predominantly of CD3+CD8+ T-cells. Islets with insulitis were found in close proximity to islets devoid of insulin-positivity; such pseudo-atrophic islets were present in multiple small foci scattered throughout the pancreatic tissue or were found to be distributed with a lobular pattern. Relative beta cell area in both single and multiple autoantibody-positive donors was comparable to that in autoantibody-negative controls. In conclusion, in organ donors under age 25 years, insulitis and pseudo-atrophic islets were restricted to multiple autoantibody-positive individuals allegedly at high risk of developing symptomatic type 1 diabetes, in line with reports in older age groups. These observations may give further insight into the early pathogenetic events that may culminate in clinically overt disease.

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Title: Insulitis in the pancreas of non-diabetic organ donors under age 25 years with multiple circulating autoantibodies against islet cell antigens
Authors: Silke Smeets
Diedert Luc De Paep
Geert Stangé
Katrijn Verhaeghen
Bart Van der Auwera
Bart Keymeulen
Ilse Weets
Zhidong Ling
Peter in’t Veld
Frans Gorus
Publication date: 01-08-2021
Publisher: Springer Berlin Heidelberg
Keywords: Insulins
Insulins
Type 1 Diabetes
Published in: Virchows Archiv / Issue 2/2021
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-021-03055-z

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Insulitis in the pancreas of non-diabetic organ donors under age 25 years with multiple circulating autoantibodies against islet cell antigens

Abstract

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Abstract

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