Autoantibody response to islet transplantation in type 1 diabetes

Islet allotransplantation into patients with autoimmune type 1 diabetes rep resents a reexposure to autoantigen. Here, measurement of antibodies to GAD and IA-2 autoantigens before and after islet transplantation in 36 patient s (33 receiving islet plus kidney grafts with cyclosporin and steroid-based immunosuppression, and 3 receiving solitary islet transplants with mycophe nolate but cyclosporin-free immunosuppression) demonstrated marked rises in GAD antibodies within 7 days posttransplantation in 5 patients (3 receivin g islet after kidney transplants, and 2 receiving solitary islet transplant s) and within 30 days in the third patient receiving solitary islet transpl antation. GAD antibodies were of the IgG1 subclass, against major autoantig enic epitopes, and in cases of islet after kidney transplants, the response s were short-lived and not accompanied by HLA antibodies. Two of these pati ents had subsequent marked rises of IA-2 antibodies, and an additional pati ent had a marked rise in IgM-GAD antibodies 3 years after transplantation. Insulin independence was not achieved in patients with autoantibody elevati ons and was significantly less frequent in these patients. These data are c onsistent with a reactivation of autoimmunity that may be dependent on immu nosuppression therapy and is associated with impaired graft function.