Department of Kidney Disease and Transplant Immunology, Aichi Medical University School of Medicine, Nagakute, Japan,
Department of Kidney Transplantation, Aichi Medical University School of Medicine, Nagakute, Japan.
Nephron. 2020;144 Suppl 1:2-6. doi: 10.1159/000510747. Epub 2020 Nov 25.
Antibody-mediated rejection (ABMR) in organ transplantation has been recognized as the main cause of graft rejection. Binding of donor-specific HLA antibody (DSA) and A/B blood type antibody on graft endothelial cells causes complement-dependent tissue damage. C4d, a product of the complement cascade, has long been an indicator of graft tissue damage in graft endothelial cells. By contrast, recent evidences indicated histological findings of ABMR without C4d deposition in many cases and Banff classification criteria included a category of C4d-negative ABMR. Several mechanisms have been proposed for complement-independent tissue injury in the presence of DSA. It is well known that activated monocytes and macrophages infiltrate into graft tissues. The inflammatory environment triggered by the binding of DSA to endothelial cells alone can induce an allo-reaction of CD4 T-cells via graft endothelial cell HLA-class II. Accommodation is a condition that no rejections occur even in the presence of an antibody against donor organs and becomes attracting considerable attention as a therapeutic strategy to acquire long-term survival of the transplanted organs. Several recent publications have suggested some mechanistic insights about graft accommodation, including the upregulation of antioxidant, anti-apoptotic, and complement regulatory proteins genes via activation of PI3K/AKT survival signal or inactivation of extracellular signal-regulated protein kinase pro-inflammatory signals after DSA and anti-A/B antibody ligation on endothelial cells.
器官移植中的抗体介导的排斥反应（ABMR）已被认为是移植物排斥的主要原因。供体特异性 HLA 抗体（DSA）和 A/B 血型抗体与移植物内皮细胞结合，导致补体依赖性组织损伤。补体级联的产物 C4d 长期以来一直是移植物内皮细胞中移植物组织损伤的指标。相比之下，最近的证据表明，在许多情况下，ABMR 存在组织病理学发现而无 C4d 沉积，Banff 分类标准包括 C4d 阴性 ABMR 类别。已经提出了几种用于在存在 DSA 的情况下进行补体非依赖性组织损伤的机制。众所周知，激活的单核细胞和巨噬细胞浸润到移植物组织中。DSA 与内皮细胞结合所引发的炎症环境可以通过 HLA-II 类抗原诱导 CD4 T 细胞的同种反应。容纳是一种即使存在针对供体器官的抗体也不会发生排斥反应的情况，作为获得移植器官长期存活的治疗策略，已引起相当大的关注。最近的几项出版物提出了一些关于移植物容纳的机制见解，包括通过激活 PI3K/AKT 存活信号或在 DSA 和内皮细胞上的抗-A/B 抗体结合后使细胞外信号调节蛋白激酶促炎信号失活，上调抗氧化、抗凋亡和补体调节蛋白基因。
