Poster Presentation The 13th International Congress of the Immunology of Diabetes Society 2013

Insulitis in type 1 diabetes (#69)

Martha Campbell-Thompson 1 , Irina Kusmartseva 1 , Tiffany Heiple 1 , Ann Fu 1 , Cathy Sun 1 , Jayne Moraski 1 , Suzy Ball 1 , Clive Wasserfall 1 , John Kaddis 2 , Des Schatz 1 , Alberto Pugliese 3 , Mark Atkinson 1
  1. University of Florida, Gainesville, FL, United States
  2. City of Hope, Duarte, CA, USA
  3. University of Miami, Miami, FL, USA

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.


  1. Campbell-Thompson, ML et. al. The diagnosis of insulitis in human type 1 diabetes. Diabetologia 2013.