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 (μg/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.
Keywords: Multiple sclerosis; biomarkers; cerebrospinal fluid; complement; neuromyelitis optica.
Reference
Zelek, W. M., Fathalla, D., Morgan, A., Touchard, S., Loveless, S., Tallantyre, E., ... & Morgan, B. P. (2020). Cerebrospinal fluid complement system biomarkers in demyelinating disease. Multiple Sclerosis Journal, 26(14), 1929-1937.