Neurofilament levels are associated with blood–brain barrier integrity, lymphocyte extravasation, and risk factors following the first demyelinating event in multiple sclerosis

Tomas Uher, Mason McComb, Shery Galkin, Barbora Srpova, Johanna Oechtering, Christian Barro, Michaela Tyblova, Niels Bergsland, Jan Krasensky, Michael Dwyer, Eva Kubala Havrdova, Helena Posova, Manuela Vaneckova, Robert Zivadinov, Dana Horakova, Jens Kuhle, Murali Ramanathan

Research output: Contribution to journalArticle

Abstract

Background: Increased blood brain barrier (BBB) permeability, CNS inflammation and neuroaxonal damage are pathological hallmarks in early multiple sclerosis (MS). Objective: To investigate the associations of neurofilament light chain (NfL) levels with measures of BBB integrity and central nervous system (CNS) inflammation in MS during the first demyelinating event. Methods: Blood and cerebrospinal fluid (CSF) were obtained from 142 MS (McDonald 2017) treatment-naive patients from the SET study (63% female; age: 29.7 ± 7.9 years) following the disease onset. NfL, albumin, immunoglobulin G (IgG), and immunoglobulin M (IgM) levels were measured in CSF and blood samples. Albumin quotient was computed as a marker of BBB integrity. Immune cell subset counts in CSF were measured using flow cytometry. MS risk factors, such as Human leukocyte antigen DRB1 locus gene (HLA DRB1)*1501, anti-Epstein–Barr virus (EBV) antibodies, and 25-hydroxy vitamin D3, were also measured. Results: Higher serum NfL (sNfL) levels were associated with higher albumin quotient (p < 0.001), CSF CD80+ (p = 0.012), and CD80+ CD19+ (p = 0.015) cell frequency. sNfL levels were also associated with contrast-enhancing and T2 lesions on brain magnetic resonance imaging (MRI; all p ⩽ 0.001). Albumin quotient was not associated with any of the MS risk factors assessed. sNfL levels were associated with anti-EBV viral capsid antigen (VCA) IgG levels (p = 0.0026). Conclusion: sNfL levels during the first demyelinating event of MS are associated with greater impairment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI.

Original languageEnglish
JournalMultiple Sclerosis Journal
DOIs
Publication statusAccepted/In press - Jan 1 2020

Keywords

  • biomarker
  • blood–brain barrier
  • Epstein–Barr virus
  • MRI
  • multiple sclerosis
  • Neurofilament light chain

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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    Uher, T., McComb, M., Galkin, S., Srpova, B., Oechtering, J., Barro, C., Tyblova, M., Bergsland, N., Krasensky, J., Dwyer, M., Havrdova, E. K., Posova, H., Vaneckova, M., Zivadinov, R., Horakova, D., Kuhle, J., & Ramanathan, M. (Accepted/In press). Neurofilament levels are associated with blood–brain barrier integrity, lymphocyte extravasation, and risk factors following the first demyelinating event in multiple sclerosis. Multiple Sclerosis Journal. https://doi.org/10.1177/1352458520912379