title: Pretransplantation GAD-autoantibody status to guide prophylactic antibody induction therapy in simultaneous pancreas and kidney transplantation.
abstract: 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.
authors.affiliation: 1 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. 2 Department of Immunohematology & Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. 3 Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. 4 Department of Immunology of Diabetes Unit, San Raffaele Scientific Institute Milan, Italy. 5 Center for Regenerative Therapies Dresden, Dresden, Germany. 6 Address correspondence to: Johan W. de Fijter, M.D., Ph.D., Department of Nephrology, Leiden University Medical Center, C3-P22, P.O. Box 9600, NL-2300 RC Leiden, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Ringers
authors.forename: Cornelis R
authors.initials: CR
authors.lastname: van der Torren
authors.forename: Pieter
authors.initials: P
authors.lastname: van de Linde
authors.forename: Paul J M
authors.initials: PJ
authors.lastname: van der Boog
authors.forename: Marko J K
authors.initials: MJ
authors.lastname: Mallat
authors.forename: Ezio
authors.initials: E
authors.lastname: Bonifacio
authors.forename: Bart O
authors.initials: BO
authors.lastname: Roep
authors.forename: Johan W
authors.initials: JW
authors.lastname: de Fijter
mesh_terms: D000208:Acute Disease; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D001323:Autoantibodies / Q000097:blood*; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000961:Antilymphocyte Serum; D001323:Autoantibodies; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D005968:Glutamate Decarboxylase