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.

Brain and Mind Center University of Sydney Sydney Australia

Cedars Sinai Medical Center Los Angeles CA USA

Department of Neurology Heinrich Heine University Düsseldorf Germany

Department of Neurology Medical University of Vienna Vienna Austria

Department of Neurology Palacky University Olomouc Olomouc Czech Republic

Department of Neurology Thomas Jefferson University Hospital Philadelphia PA USA

Erasmus MC University Medical Center Rotterdam The Netherlands

Neuroimmunology National and Kapodistrian University of Athens Medical School Athens Greece

Neuromuscular Diseases Unit Department of Neurology Hospital de La Santa Creu 1 Sant Pau Barcelona Spain

Sanofi Neurology Clinical Development Cambridge MA USA

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