Objective: Multiple sclerosis (MS) is a multifactorial disease that begins in 80-85% of patients as a relapsing-remitting form (RRMS), and about 50% of patients gradually develop a secondary progressive form (SPMS). Approximately 10-20% of patients are affected primarily by the progressive form (PPMS) of this disease, which is characterised by a progressive course. This work focuses on the detection of potential protein biomarkers (CHI3L1, sNfL, CXCL13, MCP-1, MMP-2, and MMP-9) in the serum of patients with multiple sclerosis, divided according to phenotype.
Patients and methods: We detected serum (RRMS: n=40, SPMS: n=25, PPMS: n=15) concentrations of selected markers of demyelination and inflammation using ELISA and zymographic determination for accurate and reproducible recognition of individual forms of MS, as well as a comparison of their levels with a worsening of no evidence of disease activity (NEDA-3) status and patients' disability.
Results: We detected that concentrations of sNfL in the blood of patients with PMS were higher than in those with RRMS (about 46%, p<0.001). The association with a worsening of NEDA-3 status was confirmed in the RRMS group by positive correlation of sNfL and the expanded disability status scale (EDSS) score (r=0.579, p<0.01). The levels of MCP-1 protein were not significantly different in patients with the RRMS to the progressive form of MS (r=0.58, p=0.02), while the levels of CHI3L1 in both the RRMS and PMS groups were significantly increased in groups with evidence of disease activity (RRMS about 76%, p<0.001 and PMS about 62%, p<0.001).
Conclusions: Earlier and non-invasive detection of serum biomarkers and their correlations with neurological disability can help to recognise the transition from RRMS to progressive forms of MS and complement the results of clinical and radiological follow-up of the patient and potentially help in monitoring the patient's response to the treatment.