Reactivation of type 1 diabetes in patients receiving: Human fetal pancreatic tissue transplants without immunosuppression

Background. Insulin-dependent (type 1) diabetes is a cell-mediated autoimmu ne disease. Successful transplantation of human fetal pancreatic tissue int o type 1 diabetic patients must address both autoimmunity and allograft rej ection. We investigated whether humoral and cellular responses to islet ant igens could be demonstrated in the peripheral blood of type 1 diabetic subj ects receiving human fetal pancreatic tissue transplants. Methods. We investigated peripheral blood mononuclear cell (PBMC) responses , using cellular immunoblotting, and autoantibody responses to islet protei ns, before transplantation and at 3-month intervals after transplantation. Our study population included nine long-term type 1 diabetes patients (mean disease duration of 21 years) receiving human fetal pancreatic tissue subc utaneously into the abdominal wall without immunosuppression, Results. Before transplantation, all nine subjects tested negative for isle t cell autoantibody (ICA), and seven of nine subjects tested positive for g lutamic acid decarboxylase autoantibody (GADAb). After transplantation, all subjects became ICA(+), and the two patients who were GADAb(-) before tran splantation, became GADAb(+) after transplantation. Maximum PBMC reactivity to separated human fetal pancreatic proteins was observed in four patients at 3 months, in one patient at 6 months, in two patients at 9 months, and in one patient at 12 months after transplantation, One subject, who had PBM C reactivity to multiple islet proteins before transplantation, continued t o respond to multiple islet proteins throughout the study, Conclusions. We conclude that the development in the peripheral blood of IC A, GADAb, and PBMC reactivity to human fetal pancreatic proteins in the tra nsplant recipients is most consistent with reactivation of the type 1 diabe tes disease process.