Department of Surgery, University Medical Center Groningen, Groningen, Netherlands.
Department of Nephrology, Leiden University Medical Center, Leiden, Netherlands.
Front Immunol. 2019 Feb 27;10:329. doi: 10.3389/fimmu.2019.00329. eCollection 2019.
Over the last decade, striking progress has been made in the field of organ transplantation, such as better surgical expertise and preservation techniques. Therefore, organ transplantation is nowadays considered a successful treatment in end-stage diseases of various organs, e.g. the kidney, liver, intestine, heart, and lungs. However, there are still barriers which prevent a lifelong survival of the donor graft in the recipient. Activation of the immune system is an important limiting factor in the transplantation process. As part of this pro-inflammatory environment, the complement system is triggered. Complement activation plays a key role in the transplantation process, as highlighted by the amount of studies in ischemia-reperfusion injury (IRI) and rejection. However, new insight have shown that complement is not only activated in the later stages of transplantation, but already commences in the donor. In deceased donors, complement activation is associated with deteriorated quality of deceased donor organs. Of importance, since most donor organs are derived from either brain-dead donors or deceased after circulatory death donors. The exact mechanisms and the role of the complement system in the pathophysiology of the deceased donor have been underexposed. This review provides an overview of the current knowledge on complement activation in the (multi-)organ donor. Targeting the complement system might be a promising therapeutic strategy to improve the quality of various donor organs. Therefore, we will discuss the complement therapeutics that already have been tested in the donor. Finally, we question whether complement therapeutics should be translated to the clinics and if all organs share the same potential complement targets, considering the physiological differences of each organ.
在过去的十年中，器官移植领域取得了显著的进展，例如更好的手术技术和保存技术。因此，器官移植现在被认为是治疗各种终末期器官疾病（如肾脏、肝脏、肠道、心脏和肺部）的一种成功方法。然而，仍然存在一些障碍，阻止供体移植物在受体内长期存活。免疫系统的激活是移植过程中的一个重要限制因素。作为这种促炎环境的一部分，补体系统被触发。补体激活在移植过程中起着关键作用，这一点在缺血再灌注损伤（IRI）和排斥反应的大量研究中得到了强调。然而，新的研究表明，补体不仅在移植的后期阶段被激活，而且在供体中就已经开始激活。在已故供体中，补体的激活与已故供体器官质量的恶化有关。重要的是，由于大多数供体器官来自脑死亡供体或循环死亡后的供体。补体系统在已故供体的病理生理学中的确切机制和作用尚未得到充分揭示。这篇综述提供了对（多）器官供体中补体激活的当前知识的概述。靶向补体系统可能是改善各种供体器官质量的一种有前途的治疗策略。因此，我们将讨论已经在供体中进行测试的补体治疗方法。最后，我们质疑是否应该将补体治疗方法转化为临床实践，以及考虑到每个器官的生理差异，所有器官是否具有相同的潜在补体靶点。
