Complement in the Initiation and Evolution of Rheumatoid Arthritis.
Complement in the Initiation and Evolution of Rheumatoid Arthritis.
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DOI：
10.3389/fimmu.2018.01057
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发表时间：
2018
影响因子：
7.3
通讯作者：
Banda NK
中科院分区：
文献类型：
--
作者：
Holers VM;Banda NK
补体系统是免疫系统的重要组成部分，在许多保护性免疫过程中发挥核心作用，包括循环免疫复合体的处理和清除、识别外来抗原、调节体液和细胞免疫、清除凋亡和死亡细胞、参与损伤解决和组织再生过程。然而，与这些有益的作用形成鲜明对比的是，补体激活未得到充分控制是人类炎症和自身免疫性疾病的基础，包括以软骨、骨骼和滑膜为靶点的类风湿性关节炎(RA)。最近对这种疾病的研究表明，自身免疫反应随着时间的推移而演变为与粘膜炎症相关的无症状的临床前阶段。值得注意的是，这种疾病的实验模型已经证明，三条主要的补体激活途径中的每一条都在识别受损的关节组织中发挥着重要作用，尽管凝集素和放大途径在损伤的启动和扩大中发挥了特别重要的作用。在此，我们回顾了补体系统，并着重于其在人类类风湿关节炎患者和实验性小鼠模型中的多因素作用。这一理解对于成功地将新出现的补体疗法管道整合到RA患者的临床护理中将是重要的。
The complement system is a major component of the immune system and plays a central role in many protective immune processes, including circulating immune complex processing and clearance, recognition of foreign antigens, modulation of humoral and cellular immunity, removal of apoptotic and dead cells, and engagement of injury resolving and tissue regeneration processes. In stark contrast to these beneficial roles, however, inadequately controlled complement activation underlies the pathogenesis of human inflammatory and autoimmune diseases, including rheumatoid arthritis (RA) where the cartilage, bone, and synovium are targeted. Recent studies of this disease have demonstrated that the autoimmune response evolves over time in an asymptomatic preclinical phase that is associated with mucosal inflammation. Notably, experimental models of this disease have demonstrated that each of the three major complement activation pathways plays an important role in recognition of injured joint tissue, although the lectin and amplification pathways exhibit particularly impactful roles in the initiation and amplification of damage. Herein, we review the complement system and focus on its multi-factorial role in human patients with RA and experimental murine models. This understanding will be important to the successful integration of the emerging complement therapeutics pipeline into clinical care for patients with RA.