Division of Transplantation Immunology & Mucosal Biology, MRC Centre for Transplantation, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, London, United Kingdom.
Curr Opin Organ Transplant. 2014 Feb;19(1):8-13. doi: 10.1097/MOT.0000000000000037.
To provide the reader with an up-to-date comprehensive review of recent findings that highlight advances describing how proteins of the complement cascades contribute to the pathogenesis of solid organ rejection. The review is focussed mainly on renal transplantation.
Of note are recent advances in elucidating the interactions between anaphylatoxins and their receptors in organ transplantation; there is evidence of direct engagement of C5aR on donor tubules and in addition, mechanisms by which the allostimulatory capacity of dendritic cells is modulated by complement are more fully understood. Activation of the lectin pathway is increasingly implicated in allograft rejection and the role of complement in modulating regulatory T cells is being vigorously investigated. As an alternative to systemic complement inhibition, there is continued focus on the design of targeted anti-complement therapies, directed to the donor organ.
Complement has evolved as the first line of defence against pathogens, employing well defined effector mechanisms to rapidly remove infectious material. However, complement effector mechanisms are also triggered during inflammation associated with solid organ transplantation. Hence, complement has a significant role in mediating donor organ injury during both the initial ischaemia/reperfusion phase and the subsequent adaptive immune responses. Research on mechanisms of complement-mediated injury in transplantation provide a basis for the development of therapies that are aimed at transiently blocking complement activation at the site of injury, whereas leaving systemic anti-bacterial complement effector mechanisms intact.
为读者提供最新的综合评述，重点阐述补体级联蛋白在实体器官排斥反应发病机制中的作用的研究进展。本综述主要集中在肾移植方面。
值得注意的是，近年来在阐明补体级联蛋白与其受体在器官移植中的相互作用方面取得了新进展；有证据表明 C5aR 直接与供体小管相互作用，此外，补体调节树突状细胞的共刺激能力的机制也得到了更充分的理解。凝集素途径的激活越来越多地与同种异体移植物排斥反应有关，并且正在积极研究补体在调节调节性 T 细胞中的作用。作为系统抑制补体的替代方法，人们继续关注针对供体器官的靶向抗补体治疗的设计。
补体作为抵御病原体的第一道防线而进化，采用明确的效应机制来快速清除感染物质。然而，在与实体器官移植相关的炎症过程中，补体效应机制也会被触发。因此，补体在介导供体器官损伤中具有重要作用，包括在初始缺血/再灌注阶段和随后的适应性免疫反应期间。对补体介导的损伤机制的研究为开发旨在瞬时阻断损伤部位补体激活的治疗方法提供了基础，同时保留了系统的抗细菌补体效应机制。
