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

• DOI: 10.1007/s00428-021-03055-z
• Publication Date: 2021-02-19T08:32:17Z
• 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
• Keywords: Male; Adolescent; Islets of Langerhans Transplantation; CD8-Positive T-Lymphocytes; Donor Selection; Young Adult; 03 medical and health sciences; Insulin-Secreting Cells; Humans; Antigens; Child; Quality Of Life; BELCRO registry; Autoantibodies; Cell Proliferation; 0303 health sciences; Age Factors; Infant; Tissue Donors; 3. Good health; Crohn's disease; Diabetes Mellitus, Type 1; Case-Control Studies; Child, Preschool; Original Article; Female; health literacy; type 1 diabetes mellitus; Biomarkers

AbstractAutoantibodies 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.