Baseline serum neurofilament light chain levels differentiate aggressive from benign forms of relapsing–remitting multiple sclerosis: a 20-year follow-up cohort

Abstract

Background and objectives Serum biomarkers are emerging as useful prognostic tools for multiple sclerosis (MS); however, long-term studies are lacking. We aimed to evaluate the long-term prognostic value of the serum levels of neurofilament light chain (NfL), total tau, glial fibrillary acidic protein (GFAP), and chitinase 3-like-1 (CHI3L1) measured close to the time of MS onset. Methods In this retrospective, exploratory, observational, case and controls study, patients with relapsing–remitting MS (RRMS) with available baseline serum samples and prospectively follow-up in our MS unit for a long time were selected based on their clinical evolution to form two groups: (1) a benign RRMS (bRRMS) group, defined as patients with an Expanded Disability Status Scale (EDSS) score of ≤ 3 at ≥ 10 years of follow-up; (2) an aggressive RRMS (aRRMS) group, defined as patients with an EDSS score of ≥ 6 at ≤ 15 years of follow-up. An age-matched healthy control (HC) group was selected. NfL, total tau, and GFAP serum levels were quantified using a single-molecule array (SIMOA), and CHI3L1 was quantified using ELISA. Results Thirty-one patients with bRRMS, 19 with aRRMS, and 10 HC were included. The median follow-up time from sample collection was 17.74 years (interquartile range, 14.60–20.37). Bivariate and multivariate analyses revealed significantly higher NfL and GFAP levels in the aRRMS group than in the bRRMS group. A receiver operating characteristic curve analysis identified serum NfL level as the most efficient marker for distinguishing aRRMS from bRRMS. Discussion This proof-of-concept study comparing benign and aggressive RRMS groups reinforces the potential role of baseline NfL serum levels as a promising long-term disability prognostic marker. In contrast, serum GFAP, total tau, and CHI3L1 levels demonstrated a lower or no ability to differentiate between the long-term outcomes of RRMS.

The Role of Glial Fibrillary Acidic Protein as a Biomarker in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Meta-Analysis

“…A meta-analysis of eight studies evaluating sGFAP in 776 PwMS and 348 HCs revealed a statistically significant increase in sGFAP in PwMS compared to in the HCs (SMD = 0.54, 95% CI: 0.1 to 0.99, p-value = 0.02, I 2 = 90%) (Figure 2B). [11,14,15,18,[36][37][38][39]41,42,[44][45][46], (B) serum sample [14,49,54,57,63,64,66,71].…”

“…According to the meta-analysis of six studies measuring the sGFAP level of 265 PMS and 490 RRMS patients, a significantly increased sGFAP was found in PMS patients compared to in RRMS patients (SMD = 0.5, 95% CI: 0.25 to 0.75, p-value < 0.001, I 2 = 53%) (Table 2). [11,14,15,18,[36][37][38][39]41,42,[44][45][46], (B) serum sample [14,49,54,57,63,64,66,71].…”

“…Figure 2. Forest plot of the meta-analysis of pooled standard mean difference of glial fibrillary acidic protein level between people with multiple sclerosis and healthy controls: (A) cerebrospinal fluid sample[11,14,15,18,[36][37][38][39]41,42,[44][45][46], (B) serum sample[14,49,54,57,63,64,66,71].…”

Value contribution of blood-based neurofilament light chain as a biomarker in multiple sclerosis using multi-criteria decision analysis

“…Due to the high variability of MS, in which the disease can manifest very differently between individuals and over time in the same patient, clinical and radiological markers may not be specific or sensitive enough to capture the full range of changes in terms of inflammation and neurodegeneration ( 7 ). Assessment and quantification of inflammatory activity and neurodegeneration are essential to establish the severity of the disease, the long-term prognosis, the need for treatment, the treatment option and the individual response to the selected treatment, as well as the achievement of therapeutic goals ( 7 , 8 ).…”