Understanding immunopathogenic mechanisms of beta cell loss in type 1 diabetes is crucial for prevention and therapeutic strategies. The purpose of this report is to provide data from JDRF nPOD organ donors with insulitis based on a recent consensus statement for the diagnosis of insulitis (Diabetologia, 2013).
Pancreatic sections from organ donors were stained by H&E and immunohistochemistry to define islet beta and alpha cells and CD3+ T cells. Sections were required to demonstrate remnant beta cells within islets as well as having pseudoatrophic islets (insulin- glucagon+). Islet inflammation was determined herein using the criteria of ≥ 6 CD3+ cells adjacent to or within 3 islets in a given section. Serial sections were then examined for insulin positivity in the corresponding insulitic islets and percentage insulin+ insulitic islets to total insulitic islets determined.
Thirteen T1D organ donors had consensus criteria for insulitis. Nine of the 13 donors had the high risk HLA allele (DR03, 04, 03/04). Eight donors had insulinoma-associated autoantibodies (IA-2A) that were present with a second autoantibody (multiple autoantibody positive). The highest proportions of insulitic islets (8-9%) were observed in donors having diabetes duration ≤1 year, however insulitis was still detected in those following 7-12 years disease duration (1-4.3%). The proportion of insulitic islets with beta cells varied widely (43% ± 8.0%, 0-100% range).
These data show a low overall insulitis rate with HLA high risk alleles and multiple autoantibodies in most donors. The heterogenity in insulin+ insulitis lesions could be partially explained by the paucity in infiltrating cells with assessment at a single section plane. This heterogenity parallels that of the well-appreciated lobular heterogenity in beta cell loss and underscores need for better understanding of pathogenic mechanisms to account for the sporadic and chronic destruction of beta cells in T1D.