A U.K. group has investigated 31 biomarkers for their potential utility in the diagnosis and prognosis of multiple sclerosis (Kodosaki et al. J Neuroinflamm 2024;21:52). The biomarkers examined included neurofilament-light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase-3-like-1 protein (CHi3L1), pro-and anti-inflammatory cytokines (e.g. IL-6, IL-10), chemokines (e.g. CXCL12), complement proteins (e.g. C3, C5) and proteins in other pathways relevant to MS (e.g. vitamin D binding protein). CSF and serum samples were obtained from 77 people being investigated for a demyelinating condition and 80 controls.
For diagnostic purposes, levels of seven serum biomarkers were significantly different in MS patients compared to non-MS controls: osteopontin, vitamin D binding protein, complement proteins (Factor B, C5, iC3b), C-reactive protein, and NfL. The greatest differences between MS and controls were seen for serum levels of NfL (1.6-fold higher), and osteopontin (1.54-fold higher). NfL is a marker of neuroaxonal damage; serum levels have been shown to increase prior to MS diagnosis (Bjornevik et al. JAMA Neurol 2020;77:58-64). Osteopontin is a cytokine produced by lymphocytes and macrophages and is a marker of innate and adaptive immune activation.
Eight CSF biomarkers were also expressed differently in MS vs. controls: CHi3L1, soluble CD27 (associated with T cell activation), NfL, osteopontin, and four complement proteins (C5, iC3b, C9 and TCC). The greatest differences between MS and controls were seen for CSF levels of sCD27 (4.1-fold higher), NfL (3.4-fold higher) and iC3b (2.6-fold higher). A panel of six biomarkers (osteopontin, NfL, iC3b, monocyte chemoattractant protein [MCP]-1, CCL27) was highly useful in differentiating MS from non-MS controls.
The serum biomarkers that were most useful in predicting time to EDSS 6 were the complement protein C1inh/C1s and sCD27. The prognostic value was increased when up to four serum biomarkers were used (CCL27 + Factor I + osteopontin + C1inh/C1s). For predicting time to next relapse, up to six biomarkers were highly prognostic (C1inh/C1s + C3 + Factor H + CXCL12 + sCD27 + vitamin D binding protein). A noteworthy finding was the importance of complement activation to MS progression.
Previous studies have reported that a biomarker panel was useful for MS diagnosis and prognosis. For example, the combination of CHi3L1 + three chemokines (CXC motif ligand 10, 12 and 13) was reported to be predictive of CIS conversion to MS (Lucchini et al. Mol Neurobiol 2023;60:36-50).
A novel finding of the present study was that a panel of serum biomarkers was as predictive as CSF biomarkers, providing clinicians with a less invasive tool for MS diagnosis and prognosis.