aUniversité Paris Descartes, France bINSERM, Unité U1013, France cTransplantation Rénale Adulte, Hôpital Necker Enfants Malades, France dImmunologie Biologique, Hôpital Necker Enfants Malades, Paris, France.
Curr Opin Organ Transplant. 2010 Dec;15(6):709-15. doi: 10.1097/MOT.0b013e3283402cf4.
In sensitized kidney transplant recipients, whose number is continuously growing, the negative impact of antibody-mediated rejection is being increasingly recognized. The purpose of this review is to summarize the state of knowledge about the mechanisms of alloantibody production. We will also report the most recent clinical results of current immunosuppressive protocols - either preventive or curative - in this population.
Even if progress in access to transplantation and short-term graft survival has been made in sensitized patients using therapeutic strategies targeting both alloantibodies (plasmapheresis and/or intravenous globulins) and B cells (CD20 antibodies), antibody-mediated rejection remains a critical issue frequently compromising renal function and middle-term graft survival. The partial efficacy of such strategies and the presence in sensitized patients of both peripheral memory B cells and bone marrow plasma cells capable of alloantibody synthesis in vitro suggest that, in vivo, alloantibody production most likely involves both cell types, not equally targeted by CD20 antibody-based therapies.
The need for improved strategies of prevention/treatment of antibody-mediated rejection, have led, based on the actual understanding of alloantibody synthesis, to the use of drugs targeting plasma cells, that is proteasome inhibitors. Preliminary results are contrasted and highlight the necessity for controlled studies in the field of antihumoral therapies.
在不断增加的致敏肾移植受者中，抗体介导的排斥反应的负面影响正日益受到关注。本文旨在总结同种异体抗体产生的机制的研究现状。我们还将报告在该人群中当前免疫抑制方案（预防或治疗）的最新临床结果。
尽管通过针对同种异体抗体（血浆置换和/或静脉球蛋白）和 B 细胞（CD20 抗体）的治疗策略，在致敏患者中在移植准入和短期移植物存活率方面取得了进展，但抗体介导的排斥反应仍然是一个严重的问题，经常损害肾功能和中期移植物存活率。这些策略的部分疗效以及在致敏患者中存在能够体外合成同种异体抗体的外周记忆 B 细胞和骨髓浆细胞表明，在体内同种异体抗体的产生很可能涉及到这两种细胞类型，而 CD20 抗体为基础的治疗方案并不能同等地针对这两种细胞类型。
需要改进预防/治疗抗体介导排斥反应的策略，这使得人们基于对同种异体抗体合成的实际认识，开始使用针对浆细胞的药物，即蛋白酶体抑制剂。初步结果形成对比，并强调了在抗体液治疗领域进行对照研究的必要性。
