Department of Nephrology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Curr Opin Organ Transplant. 2011 Aug;16(4):425-33. doi: 10.1097/MOT.0b013e3283489a5a.
Improvements in prevention and management of cellular rejection of solid organ transplants, coupled with increasing numbers of sensitized patients, have focused attention on antibody-mediated rejection (AbMR). Complement is a critical component of AbMR, in addition to interfacing between innate and adaptive immunity and the coagulation cascade. This article reviews complement biology and strategies to overcome complement in AbMR, cognisant that antibody can act independently of complement.
The past decade has witnessed an improvement in the prevention and treatment of AbMR as a result of solid-phase assays to determine antibody specificity, definition of histopathological criteria, and use of plasmapheresis and/or intravenous immunoglobulin (IVIG). Nonetheless, AbMR continues to impact adversely on short- and long-term graft survival. Use of B and/or T-lymphocyte-depleting therapies has not shown measurable benefit, and the need remains for therapies that deplete antibody, or provide better protection from complement-mediated damage. Disordered complement activity in human diseases such as paroxysmal nocturnal haemoglobinuria, has provided additional impetus to pursuing therapeutic complement inhibition. Preliminary data from C5 inhibition with eculizumab in the treatment and prevention of AbMR have shown promise. Trials with recombinant human inhibitors of C1 (effective in angioedema) to prevent or treat AbMR are beginning.
Despite current limitations, 'protection' of the transplant through plasmapheresis and/or IVIG enables many allografts to survive in sensitized recipients. Elucidating the pathways mediating graft acceptance, by constitutive antibody deletion, or 'accommodation' (wherein donor organ remains uninjured despite antibody binding), or other local protective mechanism(s), is an equally important challenge in the quest to overcome AbMR.
实体器官移植细胞排斥的预防和治疗得到改善，加上致敏患者数量的增加，使人们对抗体介导的排斥（AbMR）的关注集中起来。补体是 AbMR 的一个关键组成部分，除了在先天免疫和适应性免疫以及凝血级联之间发挥作用外。本文综述了补体生物学和克服 AbMR 中补体的策略，认识到抗体可以独立于补体发挥作用。
过去十年，由于固相测定法确定抗体特异性、定义组织病理学标准以及使用血浆置换和/或静脉注射免疫球蛋白（IVIG），AbMR 的预防和治疗得到了改善。尽管如此，AbMR 仍然对短期和长期移植物存活率产生不利影响。使用 B 和/或 T 淋巴细胞耗竭疗法并未显示出可衡量的益处，仍然需要能够耗竭抗体或提供更好的补体介导损伤保护的疗法。阵发性夜间血红蛋白尿等人类疾病中补体活性紊乱为寻求治疗性补体抑制提供了额外的动力。用依库珠单抗抑制 C5 在治疗和预防 AbMR 中的初步数据显示出了希望。用重组人 C1 抑制剂（对血管性水肿有效）预防或治疗 AbMR 的试验正在开始。
尽管存在当前的局限性，但通过血浆置换和/或 IVIG 对移植物进行“保护”，使许多同种异体移植物在致敏受者中得以存活。通过固有抗体缺失或“适应”（尽管有抗体结合，但供体器官仍未受损）或其他局部保护机制来阐明介导移植物接受的途径，是克服 AbMR 的一个同样重要的挑战。
