Neuromuscular Diseases Unit, Department of Neurology, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain.
Department of Neurology, Heinrich Heine University, Düsseldorf, Germany.
Neurotherapeutics. 2022 Apr;19(3):864-873. doi: 10.1007/s13311-022-01221-y. Epub 2022 Apr 4.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common, heterogeneous, immune-mediated neuropathy, characterized by predominant demyelination of motor and sensory nerves. CIDP follows a relapsing-remitting or a progressive course and causes substantial disability. The pathogenesis of CIDP involves a complex interplay of multiple aberrant immune responses, creating a pro-inflammatory environment, subsequently inflicting damage on the myelin sheath. Though the exact triggers are unclear, diverse immune mechanisms encompassing cellular and humoral pathways are implicated. The complement system appears to play a role in promoting macrophage-mediated demyelination. Complement deposition in sural nerve biopsies, as well as signs of increased complement activation in serum and CSF of patients with CIDP, suggest complement involvement in CIDP pathogenesis. Here, we present a comprehensive overview of the preclinical and clinical evidence supporting the potential role of the complement system in CIDP. This understanding furnishes a strong rationale for targeting the complement system to develop new therapies that could serve the unmet needs of patients affected by CIDP, particularly in those refractory to standard therapies.
慢性炎症性脱髓鞘性多发性神经病（CIDP）是最常见、异质性最强的免疫介导性神经病，其特征是运动和感觉神经的脱髓鞘占主导地位。CIDP 呈复发缓解或进行性病程，导致严重残疾。CIDP 的发病机制涉及多种异常免疫反应的复杂相互作用，形成促炎环境，随后对髓鞘造成损伤。尽管确切的触发因素尚不清楚，但涉及细胞和体液途径的多种免疫机制都有牵连。补体系统似乎在促进巨噬细胞介导的脱髓鞘中发挥作用。在腓肠神经活检中发现补体沉积，以及 CIDP 患者血清和脑脊液中补体激活迹象增加，提示补体参与 CIDP 的发病机制。在这里，我们全面概述了支持补体系统在 CIDP 中潜在作用的临床前和临床证据。这种理解为针对补体系统开发新疗法提供了强有力的理由，这些疗法可以满足 CIDP 患者的未满足需求，特别是那些对标准疗法有抗性的患者。
