Radboud University Nijmegen Medical Centre, Department of Nephrology, Nijmegen, The Netherlands.
Expert Opin Biol Ther. 2012 Aug;12(8):1031-42. doi: 10.1517/14712598.2012.689278. Epub 2012 May 15.
Given the central role of T cells in the alloimmune response, anti-T-cell antibodies retain a prominent place in the treatment of renal allograft rejection. During the past decades, many anti-T-cell antibodies have emerged and subsequently left the field of solid organ transplantation, but rabbit-antithymocyte globulin (ATG) and the humanized anti-CD52 monoclonal rat antibody alemtuzumab have remained.
This article reviews the literature about the use of ATG and alemtuzumab for the treatment of acute rejection after renal transplantation. Furthermore, it discusses possible side effects, including infusion reactions. A literature search using PubMed and Embase databases was undertaken using search words alemtuzumab, antithymocyte globulin, rejection, kidney and renal transplantation.
Treatment of severe or steroid-resistant renal allograft rejections with ATG is very effective, but is also associated with frequent infusion reactions and an increased incidence of infections and posttransplant lymphoproliferative disease. Alemtuzumab may prove to be an attractive alternative. It can be administered easily, is relatively cheap and nearly devoid of acute side effects, but the long-term efficacy and safety as anti-rejection treatment are currently difficult to judge. The increasing knowledge about lymphocyte subsets and their plasticity will drive the development of new, specific immunosuppression that lacks side effects of ATG and alemtuzumab. TOL101, a monoclonal antibody specifically directed against the human αβ T cell receptor, might be of potential value.
鉴于 T 细胞在同种免疫反应中的核心作用,抗 T 细胞抗体在治疗肾移植排斥反应中仍占有重要地位。在过去的几十年中,出现了许多抗 T 细胞抗体,但随后都退出了实体器官移植领域,而兔抗胸腺细胞球蛋白(ATG)和人源化抗 CD52 单克隆鼠抗体阿仑单抗仍然存在。
本文综述了 ATG 和阿仑单抗治疗肾移植后急性排斥反应的文献。此外,还讨论了可能的副作用,包括输注反应。使用 PubMed 和 Embase 数据库进行了文献检索,使用的检索词包括阿仑单抗、抗胸腺细胞球蛋白、排斥、肾脏和肾移植。
用 ATG 治疗严重或激素耐药的肾移植排斥反应非常有效,但也与频繁的输注反应、感染和移植后淋巴增生性疾病发生率增加有关。阿仑单抗可能是一种有吸引力的替代药物。它可以方便地给药,相对便宜,几乎没有急性副作用,但作为抗排斥治疗的长期疗效和安全性目前难以判断。对淋巴细胞亚群及其可塑性的认识不断提高,将推动开发缺乏 ATG 和阿仑单抗副作用的新型、特异性免疫抑制药物。针对人类 αβ T 细胞受体的单克隆抗体 TOL101 可能具有潜在价值。