Böhmig Georg A, Naesens Maarten, Viklicky Ondrej, Thaunat Olivier, Diebold Matthias, Rostaing Lionel, Budde Klemens
Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.
Nephrol Dial Transplant. 2025 Aug 1;40(8):1615-1627. doi: 10.1093/ndt/gfaf097.
Antibody-mediated rejection (AMR) remains a major cause of graft failure, with significant health and economic burden. Despite being recognized >25 years ago, AMR treatment remains unstandardized, and no therapy has gained robust regulatory approval. While uncontrolled series have shown promise, few well-designed trials exist, with most yielding negative results. In the absence of strong trial data, a Transplantation Society expert consensus recommended potential treatment options with low levels of evidence, tailored to clinical phenotypes. Here, we re-evaluate the current evidence for AMR treatment decisions. We conclude that steroids, rituximab, bortezomib, and interleukin-6 (IL-6) antagonists lack sufficiently robust evidence to support their use in AMR. For early AMR, antibody depletion using immunoadsorption could be considered as an alternative to plasmapheresis. High-dose intravenous immunoglobulin (IVIG) may be added, though the supporting evidence remains limited. While previous trials primarily targeted the cause of AMR, recent data on the successful reversal of AMR activity by CD38 antibodies-particularly recent phase 2 trial results-suggest that targeting the cellular inflammation resulting from antibody binding to the endothelium could be a rational approach. Along these lines, in severe early AMR, complement inhibition may also be an option. Ongoing phase 2 trials evaluating prolonged courses of high-dose IVIG, the neonatal Fc receptor blocker efgartigimod, the tyrosine kinase inhibitor fostamatinib, and the complement inhibitor BIVV020, along with phase 3 trials of the anti-IL-6 receptor antibody tocilizumab and the CD38 antibody felzartamab, offer hope for effective, approved therapies targeting different aspects of AMR pathobiology.
抗体介导的排斥反应（AMR）仍然是移植失败的主要原因，带来了巨大的健康和经济负担。尽管AMR在25年前就已被认识到，但其治疗仍未标准化，且没有疗法获得强有力的监管批准。虽然非对照系列研究显示出一定前景，但精心设计的试验很少，大多数试验结果为阴性。在缺乏有力试验数据的情况下，移植学会专家共识推荐了证据水平较低的潜在治疗方案，这些方案根据临床表型进行了调整。在此，我们重新评估当前用于AMR治疗决策的证据。我们得出结论，类固醇、利妥昔单抗、硼替佐米和白细胞介素-6（IL-6）拮抗剂缺乏足够有力的证据支持其在AMR中的使用。对于早期AMR，可考虑使用免疫吸附进行抗体清除，作为血浆置换的替代方法。尽管支持证据仍然有限，但可添加大剂量静脉注射免疫球蛋白（IVIG）。虽然先前的试验主要针对AMR的病因，但最近关于CD38抗体成功逆转AMR活性的数据——特别是最近的2期试验结果——表明，针对抗体与内皮细胞结合导致的细胞炎症可能是一种合理的方法。据此，在严重的早期AMR中，补体抑制也可能是一种选择。正在进行的评估大剂量IVIG延长疗程、新生儿Fc受体阻滞剂艾加莫德、酪氨酸激酶抑制剂福斯他替尼和补体抑制剂BIVV020的2期试验，以及抗IL-6受体抗体托珠单抗和CD38抗体费尔扎他单抗的3期试验，为针对AMR病理生物学不同方面的有效、获批疗法带来了希望。
