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治疗性补体抑制:治疗神经免疫性疾病的一种有前景的方法。

Therapeutic complement inhibition: a promising approach for treatment of neuroimmunological diseases.

作者信息

Pilch Kjara S, Spaeth Peter J, Yuki Nobuhiro, Wakerley Benjamin R

机构信息

a Department of Cell and Developmental Biology , University College London , UK.

b University of Bern, Institute of Pharmacology , Bern , Switzerland.

出版信息

Expert Rev Neurother. 2017 Jun;17(6):579-591. doi: 10.1080/14737175.2017.1282821. Epub 2017 Mar 6.

DOI:10.1080/14737175.2017.1282821
PMID:28092989
Abstract

Autoimmunity is an important cause of disease both in the central and peripheral nervous systems. Aetiologies and clinical manifestations are complex and heterogeneous. Inappropriate control of complement activation at inappropriate sites has been recognized as a major determinant in several neurological conditions, including Guillain-Barré syndrome and neuromyelitis optica. In each case pathogenesis is thought to be associated with generation of autoantibodies which upon binding guide activation of the complement system to self-tissue. Areas covered: Modulation of the complement system activation at such sites may represent a novel therapeutic approach for treatment of immune-mediated inflammatory conditions. In this review we focus on the therapeutic effects of complement inhibitors in Guillain-Barré syndrome and neuromyelitis optica and highlight recent developments within the field. Expert Commentary: Conventional first line treatment strategies in GBS and NMO have the potential disadvantage of causing widespread immunosuppressive effects. A more targeted approach may therefore be more effective and less disruptive to the immune system, especially in the case of NMO, which requires long term immunosuppression. Modulation of the complement system may hold the key and has already been shown to be of clinical benefit in other non-neurological conditions, including paroxysmal nocturnal hemoglobinuria and hereditary angioedema.

摘要

自身免疫是中枢神经系统和周围神经系统疾病的重要病因。其病因和临床表现复杂多样。在包括吉兰 - 巴雷综合征和视神经脊髓炎在内的几种神经系统疾病中,补体激活在不适当部位的控制不当已被认为是一个主要决定因素。在每种情况下,发病机制被认为与自身抗体的产生有关,这些自身抗体结合后会引导补体系统对自身组织的激活。涵盖领域:在这些部位调节补体系统激活可能代表一种治疗免疫介导的炎症性疾病的新方法。在本综述中,我们重点关注补体抑制剂在吉兰 - 巴雷综合征和视神经脊髓炎中的治疗效果,并强调该领域的最新进展。专家评论:吉兰 - 巴雷综合征和视神经脊髓炎的传统一线治疗策略存在导致广泛免疫抑制作用的潜在缺点。因此,一种更具针对性的方法可能更有效,对免疫系统的干扰也更小,特别是对视神经脊髓炎而言,它需要长期免疫抑制。补体系统的调节可能是关键,并且已经在包括阵发性夜间血红蛋白尿和遗传性血管性水肿在内的其他非神经系统疾病中显示出临床益处。

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