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Initial Results of Screening of Nondiabetic Organ Donors for Expression of Islet Autoantibodies

The Barbara Davis Center (R.G., A.P., T.S., L.Y., D.M., R.G.G., J.B., P.S., A.V., G.S.E., J.H., P.G., A.W.) and Department of Pathology (R.G.), University of Colorado at Denver and Health Science Center, Aurora, Colorado 80010; Department of Pathology (R.G.), The Children’s Hospital, Denver, Colorado 80218; and Donor Alliance (A.I., S.D.), Denver, Colorado 80246

Address all correspondence and requests for reprints to: Roberto Gianani, The Barbara Davis Center, 1775 North Ursula Street, Aurora, Colorado 80010. E-mail: roberto.gianani{at}uchsc.edu.

Context: Type 1A diabetes is characterized by a long prodromal phase during which autoantibodies to islet antigens are present. Nevertheless, we lack data on the pancreatic pathology of subjects who are positive for islet autoantibodies (to islet autoantigens GAD65, insulin, and ICA512).

Objective: In this manuscript, we describe a novel strategy in obtaining pancreata and pancreatic lymph nodes from islet autoantibody-positive organ donors that involves careful coordination among the laboratory and the organ donor provider organization.

Design: We developed a rapid screening protocol for islet autoantibodies measurement of organ donors to allow identification of positive subjects before organ harvesting. In this way we were able to obtain pancreata and pancreatic lymph nodes from subjects with and without islet autoimmunity.

Setting: The organ donors used in this study were obtained from the general community.

Subjects: The population studied consisted of 112 organ donors (age range 1 month to 86 yr, mean age 39 yr).

Main Outcome Measure: The main outcome measure of this study consisted of evaluating the pancreatic histology and identify T cells autoreactive for islet antigens in the pancreatic lymph nodes.

Results: To date we have identified three positive subjects and obtained the pancreas for histological evaluation from one of the autoantibody-positive donors who expressed ICA512 autoantibodies. Although this subject did not exhibit insulitis, lymphocytes derived from pancreatic lymph nodes reacted to the islet antigen phogrin.

Conclusion: In summary, these results indicate that it is possible to screen organ donors in real time for antiislet antibodies, characterize pancreatic histology, and obtain viable T cells for immunological studies.

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