Serum neurofilament light chain as a biomarker in multiple sclerosis: A cross-sectional observation in real-world clinical practice

Mult Scler Relat Disord. 2025 Nov:103:106637. doi: 10.1016/j.msard.2025.106637. Epub 2025 Jul 23.

Abstract

Background: Despite growing evidence on serum neurofilament light (sNfL) as a biomarker in Multiple Sclerosis (MS), its implementation and performance in clinical practice remain underexplored. This study aimed to evaluate the application of NfL testing comparing two immunoassays-the current gold-standard Simoa by Quanterix and the most recent Elecsys by Roche-in real-world conditions, moving beyond controlled research environments.

Method: This cross-sectional study recruited 97 patients with Relapsing-Remitting MS (RRMS), collecting baseline and retrospective demographic, clinical and MRI data as part of routine care. Serum NfL levels were measured using Simoa and Elecsys immunoassays and were log10-transformed. Associations between sNfL levels and outcomes were evaluated using generalized linear and binary logistic regression models, with covariate adjustments reflective of clinical conditions.

Results: Elecsys sNfL highly correlated with Simoa levels (R2≈0.891) with a strong negative bias of 88.19 %. Despite this, both assays showed that sNfL significantly associated with disease-modifying treatment, time since last relapse, Expanded Disability Status Scale, Symbol Digit Modalities Test, Timed 25-Foot Walk, brain atrophy, GD-enhancing T2 brain lesions, new or enlarging T2 brain lesions and infratentorial T2 brain lesions. Subgroup analyses showed Elecsys and Simoa sNfL models had similar performance metrics compared to clinical-only models, though Elecsys sNfL demonstrated mixed findings with some markers of disease activity (e.g. GD+ lesions) and progression (e.g. T1-hypointense, infratentorial and cervical spinal cord lesion burden).

Conclusion: Our results support the use of sNfL as a robust and informative biomarker within the real-world complexities of clinical care, with either the Elecsys or Simoa immunoassays offering reliable options.

Keywords: Biomarkers; Glial fibrillary acidic protein; MRI; Multiple sclerosis; Neurofilament light.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunoassay / methods
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting* / blood
  • Multiple Sclerosis, Relapsing-Remitting* / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting* / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting* / pathology
  • Neurofilament Proteins* / blood
  • Retrospective Studies

Substances

  • Neurofilament Proteins
  • Biomarkers
  • neurofilament protein L