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Cerebrospinal fluid complement system biomarkers in demyelinating disease
Wioleta Milena Zelek1, Dina Fathalla1, Angharad Morgan1
1Systems Immunity University Research Institute, Cardiff University, Cardiff, UK.
Background:
Multiple sclerosis (MS) can be difficult to differentiate from other demyelinating diseases, notably neuromyelitis optica spectrum disorder (NMOSD). We previously showed that NMOSD is distinguished from MS by plasma complement biomarkers.
Objective:
Here, we measure cerebrospinal fluid (CSF) complement proteins in MS, NMOSD and clinically isolated syndrome (CIS), a neurological episode that may presage MS, to test whether these distinguish NMOSD from MS and CIS.
Materials And Methods:
CSF (53 MS, 17 CIS, 11 NMOSD, 35 controls) was obtained; complement proteins (C4, C3, C5, C9, C1, C1q, Factor B (FB)), regulators (Factor I (FI), Factor H (FH), FH-Related Proteins 1, 2 and 5 (FHR125), C1 Inhibitor (C1INH), Properdin) and activation products (terminal complement complex (TCC), iC3b) were quantified by ELISA and results expressed relative to CSF total protein (microg/mg).
Results:
Compared to control CSF, (1) levels of C4, C1INH and Properdin were elevated in MS; (2) TCC, iC3b, FI and FHR125 were increased in CIS; and (3) all complement biomarkers except TCC, FHR125, Properdin and C5 were higher in NMOSD CSF. A statistical model comprising six analytes (C3, C9, FB, C1q, FI, Properdin) plus age/gender optimally differentiated MS from NMOSD.
Insights
Cerebrospinal fluid complement biomarkers can help differentiate multiple sclerosis (MS) from neuromyelitis optica spectrum disorder (NMOSD). Specific proteins in CSF distinguish these demyelinating diseases, aiding diagnosis.
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.
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