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SCREENING FOR INSULITIS IN ADULT AUTOANTIBODY-POSITIVE ORGAN DONORS.

Diabetes Research Center, Brussels Free University (VUB) and JDRF Center for Beta Cell Therapy in Diabetes, Brussels, Belgium

Correspondence: intveld{at}vub.ac.be

Objective.: 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 against islet cell antigens exhibit insulitis and/or a reduced beta cell mass.

Research Design and Methods.: Serum from 1507 organ donors (age 25-60 years) was analyzed for ICA, GADA, IA-2A and IAA. Tissue from the 62 aAb-positive donors (4.1%) and from matched controls was examined for the presence of insulitis and for the relative area of insulin-positive cells.

Results.: Insulitis was detected in two cases; it was found in 3 and 9 percent of the islets and consisted of CD3+/CD8+ T-cells and CD68+ macrophages; in one case it was associated with insulin-positive cells that expressed the proliferation 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-positive and aAb-negative donors did not show a significant difference.

Conclusions.: Insulitis was found in 2 of the 3 cases that presented at least three islet cell autoantibodies, but in none of the other 59 antibody-positive subjects or 62 matched controls. It was only detected in less than 10 percent of the islets, some of which presented signs of beta cell proliferation. No decrease in beta cell mass was detected in cases with insulitis, or in the group of antibody-positive subjects.

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