Palmisano Alessandra, Gandolfini Ilaria, Gentile Micaela, Benigno Giuseppe Daniele, Delsante Marco, D'angelo Marta, Fiaccadori Enrico, Maggiore Umberto
UO Nefrologia, Azienda Ospedaliera-Universitaria Parma.
G Ital Nefrol. 2024 Oct 9;41(Suppl 83):2024-S83.
Despite the advances in the immunosuppressive therapies and improvements in short term allograft survival, Antibody-mediated rejection (AMR) still represents the leading cause of late allograft failure in kidney transplant recipients. We present an insidious case of late active AMR that evolved into a severe chronic active antibody-mediated rejection, that we treated with a multidrug approach. Then, we review the current literature on the pathogenesis, diagnosis and treatment of AMR. Antibody-mediated rejection (AMR) typically occurs when anti-HLA donor-specific antibodies (DSA) bind to vascular endothelial cells of the kidney graft. DSAs may preexist to transplantation (preformed DSA) or develop after transplantation (de novo DSA). Pathogenetic mechanisms of AMR involve complement-dependent, and -independent inflammatory pathways that are variably activated depending on antigen and antibody characteristics, or on whether rejection develops early (0-6 months) or late (beyond 6 months) post-transplantation. The Banff classification system categorizes AMR rejection into active antibody-mediated rejection, chronic active antibody-mediated rejection, and chronic (inactive) antibody-mediated rejection. Currently, there are no approved therapies, treatment guidelines being based on low-quality evidence. Therefore, standard of care therapy is consensus-based. In early rejection, it is usually based on plasma exchange, intravenous immune globulin, anti-CD20 antibodies, while complement-inhibitor eculizumab is used in severe and/or refractory cases, treatments with. Recent evidence suggests that late AMR may be effectively treated with anti-CD38 therapy, which targets long lived plasma cells and NK cells.
尽管免疫抑制疗法取得了进展，同种异体移植短期存活率有所提高，但抗体介导的排斥反应（AMR）仍是肾移植受者晚期移植失败的主要原因。我们报告了一例隐匿性晚期活动性AMR病例，该病例进展为严重的慢性活动性抗体介导的排斥反应，我们采用了多种药物联合治疗。然后，我们回顾了当前关于AMR发病机制、诊断和治疗的文献。抗体介导的排斥反应（AMR）通常发生在抗HLA供体特异性抗体（DSA）与肾移植的血管内皮细胞结合时。DSA可能在移植前就已存在（预先形成的DSA），也可能在移植后产生（新发DSA）。AMR的发病机制涉及补体依赖性和非依赖性炎症途径，这些途径根据抗原和抗体的特性，或根据排斥反应在移植后早期（0 - 6个月）还是晚期（6个月后）发生而被不同程度地激活。班夫分类系统将AMR排斥反应分为活动性抗体介导的排斥反应、慢性活动性抗体介导的排斥反应和慢性（非活动性）抗体介导的排斥反应。目前，尚无获批的治疗方法，治疗指南基于低质量证据。因此，标准治疗方案是基于共识的。在早期排斥反应中，通常基于血浆置换、静脉注射免疫球蛋白、抗CD20抗体，而在严重和/或难治性病例中使用补体抑制剂依库珠单抗进行治疗。最近的证据表明，晚期AMR可能可以通过靶向长寿浆细胞和NK细胞的抗CD38疗法有效治疗。
