Autoantibody Response to Islet Transplantation in Type 1 Diabetes

  1. Emanuele Bosi,
  2. Simona Braghi,
  3. Paola Maffi,
  4. Miriam Scirpoli,
  5. Federico Bertuzzi,
  6. Guido Pozza,
  7. Antonio Secchi and
  8. Ezio Bonifacio
  1. Medicine and Surgery, San Raffaele Hospital Scientific Institute, Milan, Italy; the University of Milan, Milan, Italy; and the University San Raffaele Vita-Salute, Milan, Italy

    Abstract

    Islet allotransplantation into patients with autoimmune type 1 diabetes represents a reexposure to autoantigen. Here, measurement of antibodies to GAD and IA-2 autoantigens before and after islet transplantation in 36 patients (33 receiving islet plus kidney grafts with cyclosporin and steroid-based immunosuppression, and 3 receiving solitary islet transplants with mycophenolate but cyclosporin-free immunosuppression) demonstrated marked rises in GAD antibodies within 7 days posttransplantation in 5 patients (3 receiving islet after kidney transplants, and 2 receiving solitary islet transplants) and within 30 days in the third patient receiving solitary islet transplantation. GAD antibodies were of the IgG1 subclass, against major autoantigenic epitopes, and in cases of islet after kidney transplants, the responses were short-lived and not accompanied by HLA antibodies. Two of these patients had subsequent marked rises of IA-2 antibodies, and an additional patient had a marked rise in IgM-GAD antibodies 3 years after transplantation. Insulin independence was not achieved in patients with autoantibody elevations and was significantly less frequent in these patients. These data are consistent with a reactivation of autoimmunity that may be dependent on immunosuppression therapy and is associated with impaired graft function.

    Footnotes

    • Address correspondence and reprint requests to Emanuele Bosi, MD, Department of Medicine, San Raffaele Hospital Scientific Institute, Via Olgettina, 60, 20132 Milan, Italy. E-mail: bosi.emanuele{at}hsr.it.

      Received for publication 21 May 2001 and accepted in revised form 31 July 2001.

      ALG, antilymphocyte; ATG, antithymocyte; GADA, antibodies to GAD; IA, antibodies to insulin; IA-2A, antibodies to IA-2; IEQ, islet equivalents.

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