Cerebrospinal fluid complement system biomarkers in demyelinating disease

Area of Science:

• Neuroimmunology
• Biomarker Discovery
• Complement System Research

Background:

• Multiple sclerosis (MS) diagnosis can be challenging due to overlap with other demyelinating diseases like neuromyelitis optica spectrum disorder (NMOSD).
• Previous research identified plasma complement biomarkers distinguishing NMOSD from MS.
• This study investigates cerebrospinal fluid (CSF) complement biomarkers for NMOSD differentiation.

Purpose of the Study:

• To assess CSF complement proteins for distinguishing NMOSD from MS and clinically isolated syndrome (CIS).
• To identify specific complement biomarkers in CSF that can aid in diagnosing NMOSD.

Main Methods:

• CSF samples from patients with MS, CIS, NMOSD, and controls were analyzed.
• Quantification of various complement proteins, regulators, and activation products using ELISA.
• Results were normalized to CSF total protein concentration.

Main Results:

• Elevated levels of C4, C1 Inhibitor (C1INH), and Properdin were observed in MS CSF compared to controls.
• Increased levels of Terminal Complement Complex (TCC), iC3b, Factor I (FI), and FH-Related Proteins 1, 2 and 5 (FHR125) were found in CIS CSF.
• Most complement biomarkers were elevated in NMOSD CSF, with notable exceptions.
• A statistical model using six analytes (C3, C9, Factor B (FB), C1q, FI, Properdin) and demographic data effectively differentiated MS from NMOSD.

Conclusions:

• CSF complement profiles differ across MS, CIS, and NMOSD.
• Specific CSF complement biomarkers show potential for differentiating NMOSD from MS and CIS.
• A combination of complement analytes and demographic factors offers a robust method for distinguishing MS from NMOSD.