Longitudinal Changes in Neuroaxonal and Inflammatory CSF Biomarkers in Multiple Sclerosis Patients Undergoing Interferon Beta Therapy

Abstract

Background/Objective: Neurofilament light chain (Nf-L), neurofilament heavy chain (Nf-H), and chitinase 3-like 1 (CHI3L1) are cerebrospinal fluid (CSF) biomarkers of neuroaxonal damage and inflammation in multiple sclerosis (MS). Their longitudinal response to disease-modifying therapies and association with clinical and radiological outcomes remain incompletely understood. The aim of this study is to evaluate the impact of interferon beta (IFN-β) therapy on CSF levels of Nf-L, Nf-H, and CHI3L1 in early relapsing-remitting MS (RRMS) and assess their association with long-term clinical outcomes and MRI activity. Methods: We conducted a prospective two-year observational study involving 14 treatment-naive RRMS patients who initiated IFN-β therapy. CSF levels of Nf-L, Nf-H, and CHI3L1 were measured at baseline and after two years. Clinical disability was assessed via the Expanded Disability Status Scale (EDSS) and by studying brain MRI activity. A 15-year clinical follow-up was performed for 12 patients. Results: Nf-L levels significantly decreased after two years of IFN-β treatment (p = 0.039), while CHI3L1 levels significantly increased (p = 0.001). Nf-H levels remained stable. Nf-L and CHI3L1 levels at baseline and follow-up correlated with relapse rate and long-term EDSS. Nf-H levels correlated with EDSS scores but not with relapse or MRI activity. A trend toward a positive correlation between increasing Nf-L levels and MRI activity was observed (p = 0.07). Conclusions: CSF biomarkers demonstrate differential responses to IFN-β therapy in early RRMS. Nf-L emerges as a sensitive biomarker of treatment response and disease activity, while CHI3L1 may reflect ongoing tissue remodeling and inflammation. These findings support the utility of CSF biomarker monitoring for personalized treatment strategies in MS.

Keywords: CHI3L1; biomarkers; cerebrospinal fluid; disease-modifying therapy; interferon beta; longitudinal study; multiple sclerosis; neurofilament heavy chain; neurofilament light chain.

Figure 1

(A) Mean levels of Nf-L baseline/follow-up, which declined significantly under INF beta therapy (Wilcoxon Signed Rank test, p = 0.039) and (B) mean levels of CHI3L1 baseline/follow-up, which increased significantly under INF beta therapy (Wilcoxon Signed Rank test, p = 0.001).

Figure 2

(A) Positive correlations between EDSS baseline and Nf-H baseline levels (Spearman correlation, p = 0.017). (B) Positive correlations between EDSS follow-up and Nf-H follow-up levels (Spearman correlation, p = 0.017).

Figure 3

(A) Positive correlations between EDSS measured after 15 years and Nf-L follow-up levels (Spearman correlation, p = 0.004). (B) Positive correlations between EDSS measured after 15 years and Nf-H follow-up levels (Spearman correlation, p = 0.0001). (C) Positive correlations between EDSS measured after 15 years and CHI3L1 baseline levels (Spearman correlation, p = 0.04). (D) Positive correlations between EDSS measured after 15 years and CHI3L1 follow-up levels (Spearman correlation, p = 0.001).

Figure 4

(A) Positive correlations between relapse rate and Nf-L baseline levels (Spearman correlation, p = 0.020). (B) Positive correlations between relapse rate and Nf-L follow-up levels (Spearman correlation, p = 0.011).

Figure 5

(A) Positive correlations between relapse rate and CHI3L1 baseline levels (Spearman correlation, p = 0.020. (B) Positive correlations between relapse rate and CHI3L1 follow-up levels (Spearman correlation, p = 0.011).

Figure 6

NF-L variance and MRI activity during the follow-up period (chi square analyses test, χ² = 3.25, and p = 0.07).