Table 1.

Candidate biomarkers of therapeutic response in multiple sclerosis (MS)

Biomarker	Description	Utility in MS
NAbs	NAbs to IFNβ and natalizumab	Serum NAb testing is used to support lack of response to IFNβ or natalizumab
Fetuin-A	Secreted glycoprotein elevated in CSF of patients with MS; fetuin-A expression is associated with MS-specific brain pathology	CSF biomarker of subclinical disease activity and therapeutic response to natalizumab
Osteopontin	Matrix protein with pleiotropic functions, including pro-inflammatory cytokine; secreted by activated immune cells and abundantly expressed in MS lesions	CSF biomarker of disease activity, intrathecal inflammation, and therapeutic response to natalizumab
8-iso-PGF2α	Isoprostane byproduct of lipid peroxidation and a readout of oxidative stress; CSF 8-iso-PGF2α levels are elevated in a subset of patients with MS	CSF biomarker of oxidative stress, with possible predictive value for therapeutics targeting oxidative pathways
CXCL13	B-cell chemokine elevated in CSF of patients with MS, indicative of humoral responses	CSF biomarker of intrathecal B-cell response; potential biomarker of therapeutic response to rituximab and natalizumab
NFL/NFH	Axonal proteins elevated in CSF as a result of axonal injury	CSF NFH is a possible biomarker of accumulated axonal damage in progressive MS; CSF NFL is a possible biomarker of reduced axonal damage after natalizumab or rituximab
CHI3L1	Chitinase 3-like protein elevated in CSF of patients with CIS who convert to RRMS; expressed by microglia and astrocytes in brains of patients with MS	Prognostic CSF biomarker of conversion from CIS to RRMS; possible biomarker of therapeutic response to natalizumab

8-iso-PGF _2α 8-iso-prostaglandin F2α, CHI3L1 chitinase 3-like 1, CIS clinically isolated syndrome, CSF cerebrospinal fluid, CXCL13 chemokine (C-X-C motif) ligand 13, IFN interferon, NAbs neutralizing antibodies, NFH neurofilament heavy, NFL neurofilament light, RRMS relapsing–remitting multiple sclerosis