抗浆细胞抗体:实体器官移植中 HLA 抗体控制的新时代?

IF 8.9 2区 医学 Q1 SURGERY American Journal of Transplantation Pub Date : 2024-10-09 DOI:10.1016/j.ajt.2024.10.005
Sindhu Chandran, Flavio Vincenti
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引用次数: 0

摘要

针对浆细胞的新疗法,如抗CD38抗体和双特异性抗BCMA抗体,不仅是治疗多发性骨髓瘤的重要进展,而且有可能改变其他抗体介导疾病的治疗格局。在实体器官移植领域,针对高敏移植候选者脱敏过程中的体液同种免疫反应和移植后抗体介导的排斥反应的治疗手段落后于预防和治疗 T 细胞介导的排斥反应的进展。IVIg和血浆置换被广泛使用,但疗效有限。目前可用的抗 CD20 抗体只能部分有效地清除 B 细胞,而成熟的浆细胞则不受影响。虽然白细胞介素 6 在体液同种免疫反应和损伤中发挥着重要作用,但抑制 IL-6 所带来的益处却未能在临床试验中得到证实。即使是专门针对浆细胞开发的蛋白酶体抑制剂,由于单药疗效有限,也未能实现其承诺。本综述将重点介绍抗CD38抗体在器官移植领域的最新应用经验和潜在适用性,以及支持其用于HLA脱敏和抗体介导的排斥反应的实验数据。
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Antiplasma cell antibodies: A new era of human leukocyte antigen antibody control in solid organ transplantation.

New therapies directed against plasma cells such as anti-CD38 antibodies and the bispecific anti-B cell maturation antigen antibodies, represent not only an important advance in the treatment of multiple myeloma but have the potential to change the treatment landscape of other antibody-mediated diseases. In solid organ transplantation, the therapeutic armamentarium targeting humoral alloimmune responses in desensitization of highly sensitized transplant candidates and posttransplant antibody-mediated rejection has lagged behind advances in preventing and treating T cell-mediated rejection. Intravenous immunoglobulin and plasmapheresis are used extensively but have limited efficacy. Currently available anti-CD20 antibodies are only partially effective in achieving B cell depletion and leaving mature plasma cells untouched. Although interleukin 6 plays an important role in the humoral alloimmune response and injury, the benefits of interleukin 6 inhibition have failed to be demonstrated in clinical trials. Even proteasome inhibitors developed specifically to target plasma cells have not fulfilled their promise, due to limited efficacy as single agents. This review focuses on the recent experience with, and potential applicability of, anti-CD38 antibodies in the field of organ transplantation and experimental data supporting their use and development for human leukocyte antigen desensitization and antibody-mediated rejection.

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来源期刊
CiteScore
18.70
自引率
4.50%
发文量
346
审稿时长
26 days
期刊介绍: The American Journal of Transplantation is a leading journal in the field of transplantation. It serves as a forum for debate and reassessment, an agent of change, and a major platform for promoting understanding, improving results, and advancing science. Published monthly, it provides an essential resource for researchers and clinicians worldwide. The journal publishes original articles, case reports, invited reviews, letters to the editor, critical reviews, news features, consensus documents, and guidelines over 12 issues a year. It covers all major subject areas in transplantation, including thoracic (heart, lung), abdominal (kidney, liver, pancreas, islets), tissue and stem cell transplantation, organ and tissue donation and preservation, tissue injury, repair, inflammation, and aging, histocompatibility, drugs and pharmacology, graft survival, and prevention of graft dysfunction and failure. It also explores ethical and social issues in the field.
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