Antibody‐mediated rejection (ABMR) represents a major cause of late allograft loss in solid organ transplantation worldwide. This process is driven by donor‐specific antibodies (DSA), which develop either de‐novo or, in sensitized patients, are preformed at the time of transplantation. Effective targeting of ABMR has been hampered by a lack of robust randomized controlled trials (RCT), required for the regulatory approval of new therapeutics. In this review, we discuss the evidence behind the present “standard” of care and recent progress in the development of novel strategies targeting different aspects of the alloimmune humoral response, including naïve and memory B‐cell activation, the germinal centre reaction, plasma cell survival and antibody effector functions. In particular, we focus on co‐stimulation blockade and its combination with next‐generation proteasome inhibitors, new depleting monoclonal antibodies (anti‐CD19, anti‐BCMA, anti‐CD38, anti‐CD138), interleukin‐6 blockade, complement inhibition and DSA degradation. These treatment modalities, when used in the appropriate clinical context and combination, have the potential to finally improve long‐term allograft survival.

中文翻译：

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针对体液同种免疫反应的新策略

抗体介导的排斥反应（ABMR）是全球实体器官移植中晚期同种异体移植物丢失的主要原因。这个过程是由供体特异性抗体（DSA）驱动的，这些抗体可以从头产生，或者在致敏患者中在移植时形成。由于缺乏监管机构批准新疗法所需的强有力的随机对照试验 (RCT)，ABMR 的有效靶向受到阻碍。在这篇综述中，我们讨论了当前护理“标准”背后的证据以及针对同种免疫体液反应不同方面的新策略开发的最新进展，包括幼稚和记忆 B 细胞激活、生发中心反应、浆细胞生存和抗体效应功能。我们特别关注共刺激阻断及其与下一代蛋白酶体抑制剂、新型消耗性单克隆抗体（抗 CD19、抗 BCMA、抗 CD38、抗 CD138）、白细胞介素 6 阻断、补体抑制和DSA 降解。这些治疗方式，当在适当的临床环境和组合中使用时，有可能最终提高同种异体移植物的长期存活率。