Skip Navigation LinksHome > October 27, 2013 - Volume 96 - Issue 8 > Pretransplantation GAD-Autoantibody Status to Guide Prophyla...
doi: 10.1097/TP.0b013e3182a012cc
Clinical and Translational Research

Pretransplantation GAD-Autoantibody Status to Guide Prophylactic Antibody Induction Therapy in Simultaneous Pancreas and Kidney Transplantation

Ringers, Jan1; van der Torren, Cornelis R.2; van de Linde, Pieter1,3; van der Boog, Paul J.M.3; Mallat, Marko J.K.3; Bonifacio, Ezio4,5; Roep, Bart O.2; de Fijter, Johan W.3,6

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Background: Daclizumab and antithymocyte globulin (ATG) have been shown to reduce allograft rejection. We assessed the safety and efficacy of daclizumab or ATG prophylaxis in combination with triple immunotherapy in simultaneous pancreas-kidney transplant (SPKT) recipients.

Methods: Thirty-nine type 1 diabetic patients scheduled for primary SPKT were randomized to receive prophylactic therapy with either daclizumab or ATG. A group of 27 patients without prophylactic antibodies was used for retrospective comparison. All patients received cyclosporine and mycophenolate mofetil and gradually tapered prednisone. Autoantibodies and cellular autoreactivity were measured to assess recurrent autoreactive responses.

Results: Baseline and transplant characteristics were comparable among groups. Both daclizumab and ATG therapy resulted in a significant reduction in acute rejection episodes. The incidence of rejection episodes was significantly higher in pretransplantation GAD autoantibody-positive daclizumab-treated recipients compared with GAD autoantibody-negative or ATG-treated recipients. IA-2 islet autoantibodies showed no association with rejection. There were no significant differences between the groups for in vitro autoreactivity, clinical outcome, or functional parameters.

Conclusions: Daclizumab or ATG combined with a maintenance immunosuppressive regime consisting of cyclosporine, mycophenolate mofetil, and prednisolone were well tolerated and equally effective in reducing the incidence of acute rejection episodes in SPKT recipients. Up to 3 years, no adverse sequelae of the immunoprophylaxis or clinical and ex vivo recurrent autoimmunity were observed. We propose that the pretransplantation existence of GAD65 autoantibodies serves as a marker guiding the choice for prophylactic therapy in pancreas transplantation.

© 2013 by Lippincott Williams & Wilkins





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