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.
Transplantation. 2013 Oct 27;96(8):745-52. doi: 10.1097/TP.0b013e3182a012cc.
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.
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.
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.
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.
已有研究表明，达珠单抗和抗胸腺细胞球蛋白（ATG）可降低移植物排斥反应。我们评估了在联合胰肾移植（SPKT）受者中，达珠单抗或 ATG 预防与三联免疫疗法联合应用的安全性和疗效。
39 例 1 型糖尿病患者拟行首次 SPKT，随机分为接受达珠单抗或 ATG 预防治疗的两组。另外有 27 例无预防抗体的患者用于回顾性比较。所有患者均接受环孢素和霉酚酸酯，并逐渐减少泼尼松的用量。通过检测自身抗体和细胞自身反应性来评估是否发生复发性自身反应。
各组间的基线和移植特征具有可比性。达珠单抗和 ATG 治疗均显著降低急性排斥反应的发生率。与 GAD 抗体阴性或接受 ATG 治疗的患者相比，移植前 GAD 自身抗体阳性的达珠单抗治疗受者发生排斥反应的几率更高。IA-2 胰岛自身抗体与排斥反应无关。各组间体外自身反应性、临床结局或功能参数均无显著差异。
达珠单抗或 ATG 联合环孢素、霉酚酸酯和泼尼松的维持性免疫抑制方案，在降低 SPKT 受者急性排斥反应的发生率方面，疗效相当且均具有良好的耐受性。3 年内，未观察到免疫预防或临床和体外复发性自身免疫的不良后果。我们建议，在移植前存在 GAD65 自身抗体可作为指导选择胰腺移植预防治疗的标志物。
