OʼLeary Jacqueline G, Samaniego Millie, Barrio Marta Crespo, Potena Luciano, Zeevi Adriana, Djamali Arjang, Cozzi Emanuele
1 Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX.2 Department of Internal Medicine, Nephrology, University of Michigan, Ann Arbor, MI.3 Nephrology Department and Renal Transplant Unit, Hospital del Mar, Parc de Salut Mar, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.4 Heart and Lung Transplant Program, Department of Experimental and Specialty Medicine, Academic Hospital S. Orsola-Malpighi, University of Bologna, Bologna, Italy.5 Pathology Department, University of Pittsburgh Medical Center, Pittsburgh, PA.6 Division of Nephrology, University of Wisconsin School of Medicine and Public Health, Madison, WI.7 Transplantation Immunology, Department of Transfusion Medicine, Padua University Hospital, Padua, Italy.
Transplantation. 2016 Jan;100(1):39-53. doi: 10.1097/TP.0000000000000869.
Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance.
产生供者特异性新生抗体（dnDSA）是所有实体器官移植后急性和慢性抗体介导排斥反应及移植物丢失的主要危险因素。在本文中，我们回顾了关于个体免疫抑制剂风险及其预防dnDSA产生能力的现有数据。用兔抗胸腺细胞球蛋白进行诱导治疗可能会使中度致敏患者的dnDSA产生短期内减少。利妥昔单抗诱导治疗可能对致敏患者有益，并且在消除脱敏或抗体介导排斥反应治疗患者的抗体反应反弹方面也有益。在高危患者中使用硼替佐米进行诱导治疗值得关注，但益处尚未得到证实。在维持治疗方案中，依从性差和既往致敏的患者不适合激进的撤药方案，尤其是在没有淋巴细胞清除诱导的情况下早期停用钙调神经磷酸酶抑制剂。据报道，早期转换为雷帕霉素靶蛋白抑制剂单药治疗会增加dnDSA形成的风险，但雷帕霉素靶蛋白抑制剂与低暴露钙调神经磷酸酶抑制剂联合使用似乎不会改变风险。诱导治疗后标准风险患者早期停用类固醇治疗对dnDSA没有已知的不良影响。现有数据未显示霉酚酸对dnDSA产生有一致的影响。将dnDSA的风险降至最低需要监测依从性、进行适当的风险分层、基于风险的免疫抑制强度以及前瞻性DSA监测。
