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

Autor: Smeets S; Diabetes Research Center (DRC), Vrije Universiteit Brussel (VUB), Brussels, Belgium., De Paep DL; Diabetes Research Center (DRC), Vrije Universiteit Brussel (VUB), Brussels, Belgium.; Beta Cell Bank, UZ Brussel, Brussels, Belgium.; Department of Surgery, UZ Brussel, Brussels, Belgium., Stangé G; Diabetes Research Center (DRC), Vrije Universiteit Brussel (VUB), Brussels, Belgium., Verhaeghen K; Clinical Biology, UZ Brussel, Brussels, Belgium., Van der Auwera B; Diabetes Research Center (DRC), Vrije Universiteit Brussel (VUB), Brussels, Belgium., Keymeulen B; Diabetes Research Center (DRC), Vrije Universiteit Brussel (VUB), Brussels, Belgium., Weets I; Clinical Biology, UZ Brussel, Brussels, Belgium., Ling Z; Diabetes Research Center (DRC), Vrije Universiteit Brussel (VUB), Brussels, Belgium.; Beta Cell Bank, UZ Brussel, Brussels, Belgium., In't Veld P; Diabetes Research Center (DRC), Vrije Universiteit Brussel (VUB), Brussels, Belgium. peter.intveld@vub.be., Gorus F; Diabetes Research Center (DRC), Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Jazyk: angličtina
Zdroj: Virchows Archiv : an international journal of pathology [Virchows Arch] 2021 Aug; Vol. 479 (2), pp. 295-304. Date of Electronic Publication: 2021 Feb 16.
DOI: 10.1007/s00428-021-03055-z
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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