The role of novel therapeutic approaches for prevention of allosensitization and antibody-mediated rejection
The role of novel therapeutic approaches for prevention of allosensitization and antibody-mediated rejection
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预防同种异体致敏和抗体介导的排斥反应的新治疗方法的作用
DOI：
10.1111/ajt.15913
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发表时间：
2020-06-01
影响因子：
8.8
通讯作者：
Vo, Ashley
中科院分区：
文献类型：
--
作者：
Jordan, Stanley C.;Ammerman, Noriko;Vo, Ashley
自身免疫性疾病中致病抗体及其效应器功能的修饰或B细胞/浆细胞导向抗癌治疗的应用阐明了B细胞、浆细胞(PC)、致病抗体和补体在同种异体免疫中的生物学相关性。他们还重新燃起了人们对B细胞如何介导多种效应器功能的兴趣，这些功能包括抗体产生、抗原呈递给T细胞、共刺激以及产生免疫刺激和免疫调节细胞因子以驱动功能失调的免疫反应。目前减少同种抗体的方法只取得了一定的成功。利妥昔单抗通过靶向B淋巴细胞上的CD20用于脱敏和抗体介导的排斥反应(AMR)治疗。然而，PC不支持CD20，这很可能解释了这种方法的有限成功。静脉免疫球蛋白和血浆置换(PLEX)由于抗体反弹，成功率有限。尽管试图开发可耐受的治疗方法来管理AMR，但到目前为止，还没有一种方法被普遍接受或获得食品和药物管理局的批准。由于缺乏公认的治疗方法，由于AMR，患者的移植物存活时间往往要短得多。改变自身免疫和癌症免疫疗法的药物用途，在AMR患者的护理方面迅速产生了重要的进展。在这里，我们讨论旨在预防和治疗AMR的新兴疗法。
Modification of pathogenic antibodies and their effector functions in autoimmune diseases or use of B cell/plasma cell-directed anticancer therapies have illuminated the biologic relevance of B cells, plasma cells (PCs), and pathogenic antibodies and complement in alloimmunity. They have also rejuvenated interest in how B cells mediate multiple effector functions that include antibody production, antigen presentation to T cells, costimulation, and the production of immune stimulating and immune modulatory cytokines that drive dysfunctional immune responses. Current methods to reduce alloantibodies are only modestly successful. Rituximab is used for desensitization and antibody-mediated rejection (AMR) treatment by targeting CD20 found on B-lymphocytes. However, PCs do not express CD20, likely explaining the limited success of this approach. Intravenous immunoglobulin and plasmapheresis (PLEX) have limited success due to antibody rebound. Despite attempts to develop tolerable therapeutics for management of AMR, none, to date, have been universally accepted or obtained Food and Drug Administration approval. Lack of approved therapeutics often results in patients having a much shorter graft survival due to AMR. Repurposing drugs from autoimmunity and cancer immunotherapy has rapidly yielded important advancements in the care of AMR patients. Here we discuss emerging therapeutics aimed at prevention and treatment of AMR.