The Role of the Complement System in Chronic Inflammatory Demyelinating Polyneuropathy: Implications for Complement-Targeted Therapies

• Published in: Neurotherapeutics Vol. 19; no. 3; pp. 864 - 873
• Main Authors: Querol, Luis A., Hartung, Hans-Peter, Lewis, Richard A., van Doorn, Pieter A., Hammond, Timothy R., Atassi, Nazem, Alonso-Alonso, Miguel, Dalakas, Marinos C.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2022; Springer Nature B.V
• Subjects: Biomedical and Life Sciences; Biomedicine; Biopsy; Cerebrospinal fluid; Complement activation; Demyelination; Humans; Immune response; Inflammation; Macrophages; Macrophages - pathology; Myelin; Neurobiology; Neurology; Neuropathy; Neurosciences; Neurosurgery; Pathogenesis; Patients; Polyneuropathy; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - diagnosis; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - drug therapy; Review; Sensory neurons; Sural nerve; Complement system; Complement inhibition; Peripheral neuropathy; Demyelination; Pathogenesis; CIDP
• ISSN: 1933-7213; 1878-7479; 1878-7479
• DOI: 10.1007/s13311-022-01221-y

Summary 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.