Suchanek Ondrej, Clatworthy Menna R
Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
Cambridge University Hospitals NHS Foundation Trust, NIHR Cambridge Biomedical Research Centre, Cambridge, UK.
HLA. 2020 Dec;96(6):667-680. doi: 10.1111/tan.14092. Epub 2020 Oct 22.
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.
抗体介导的排斥反应（ABMR）是全球实体器官移植中晚期移植物丢失的主要原因。这一过程由供体特异性抗体（DSA）驱动，DSA可新发产生，或者在致敏患者中，在移植时就已存在。由于缺乏新疗法监管批准所需的强有力的随机对照试验（RCT），有效靶向ABMR一直受到阻碍。在本综述中，我们讨论了当前“标准”治疗背后的证据，以及针对同种异体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、浆细胞存活和抗体效应功能。我们特别关注共刺激阻断及其与新一代蛋白酶体抑制剂、新型清除性单克隆抗体（抗CD19、抗BCMA、抗CD38、抗CD138）、白细胞介素-6阻断、补体抑制和DSA降解的联合应用。这些治疗方式在适当的临床背景下联合使用，有可能最终提高移植物的长期存活率。
