CFHR2 supplementation mitigates pathologies of neuromyelitis optica by regulating complement activation

Area of Science:

• Neuroimmunology
• Complement System Biology

Background:

• Neuromyelitis Optica spectrum disorder (NMOSD) is a severe autoimmune condition targeting the optic nerves and spinal cord.
• The complement system's role in NMOSD pathogenesis is not fully understood, despite involvement of Aquaporin-4 antibodies (AQP4-IgG).

Purpose of the Study:

• To investigate the role of complement factor H-related protein 2 (CFHR2) in NMOSD.
• To explore CFHR2 as a potential therapeutic target for NMOSD.

Main Methods:

• Serum analysis of CFHR2 levels in NMOSD patients and correlation with disease severity (EDSS).
• Assessment of CFHR2 expression in astrocytes in vitro and in vivo NMOSD models.
• Therapeutic interventions using recombinant CFHR2 protein, AAV-mediated CFHR2 overexpression, and CFHR2-modified exosomes in NMOSD models.

Main Results:

• CFHR2 levels were significantly reduced in NMOSD patients' serum and negatively correlated with EDSS scores.
• CFHR2 expression was markedly decreased in astrocytes in NMOSD models.
• Administration of CFHR2 or its overexpression ameliorated NMOSD lesions and motor deficits by inhibiting inflammation.
• CFHR2-modified exosomes showed therapeutic potential for NMOSD.

Conclusions:

• CFHR2 is a potential biomarker and therapeutic target for NMOSD.
• Restoring CFHR2 levels or expression offers a promising strategy for treating NMOSD by modulating complement-mediated inflammation.