Ipsen Biopharm Ltd, 9 Ash Rd N, Wrexham, LL13 9UF, UK.
Department of Neurology, The Walton Centre, Lower Lane, Liverpool, L9 7LJ, UK.
J Neurol. 2021 May;268(5):1643-1664. doi: 10.1007/s00415-019-09498-4. Epub 2019 Sep 3.
The complement system is a powerful member of the innate immune system. It is highly adept at protecting against pathogens, but exists in a delicate balance between its protective functions and overactivity, which can result in autoimmune disease. A cascade of complement proteins that requires sequential activation, and numerous complement regulators, exists to regulate a proportionate response to pathogens. In spite of these mechanisms there is significant evidence for involvement of the complement system in driving the pathogenesis of variety of diseases including neuromyelitis optica spectrum disorders (NMOSD) and myasthenia gravis (MG). As an amplification cascade, there are an abundance of molecular targets that could be utilized for therapeutic intervention. Clinical trials assessing complement pathway inhibition in both these conditions have recently been completed and include the first randomized placebo-controlled trial in NMOSD showing positive results. This review aims to review and update the reader on the complement system and the evolution of complement-based therapeutics in these two disorders.
补体系统是先天免疫系统的重要组成部分。它在抵御病原体方面非常出色,但在其保护功能和过度活跃之间存在微妙的平衡,这可能导致自身免疫性疾病。补体蛋白级联反应需要连续激活,并且存在许多补体调节剂来调节对病原体的适度反应。尽管存在这些机制,但有大量证据表明补体系统参与了多种疾病的发病机制,包括视神经脊髓炎谱系疾病(NMOSD)和重症肌无力(MG)。作为一个放大级联反应,有大量的分子靶点可用于治疗干预。最近已经完成了评估这两种疾病补体途径抑制的临床试验,其中包括 NMOSD 的首次随机安慰剂对照试验,结果为阳性。这篇综述旨在回顾和更新读者关于补体系统以及这两种疾病中基于补体的治疗方法的演变。