Screening for insulitis in adult autoantibody-positive organ donors

Antibodies against islet cell antigens are used as predictive markers of type 1 diabetes, but it is unknown whether they reflect an ongoing autoimmune process in islet tissue. We investigated whether organs from adult donors that are positive for autoantibodies (&Abs) against islet cell antigens exhibit insulitis and/or a reduced P-cell mass. Serum from 1,507 organ donors (age 25-60 years) was analyzed for islet cell antibodies (ICAs), glutamate decarboxylase aAbs (GADAs), insulinoma-associated protein 2 aAbs (IA2As), and insulin aAbs. Tissue from the 62 aAb(+) donors (4.1%) and from matched controls was examined for the presence of insulitis and for the relative area of insulin(+) cells. Insulitis was detected in two cases; it was found in 3 and 9% of the islets and consisted of CD3(+)/CDS+ T-cells and CD68(+) macrophages; in one case, it was associated with insulin(+) cells that expressed the proliferatiori marker Ki67. Both subjects belonged to the subgroup of three donors with positivity for ICA, GADA, and IA-2-Ab and for the susceptible HLA-DQ genotype. Comparison of relative beta-cell area in aAb(+) and aAb(-) donors did not show a significant difference. Insulitis was found in two of the three cases that presented at least three aAbs but in none of the other 59 antibody(+) subjects or 62 matched controls. It was only detected in < 10% of the islets, some of which presented signs of P-cell proliferation. No decrease in P-cell mass was detected in cases with insulitis or in the group of antibody(+) subjects.