Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1-Associated Myelopathy and Correlates With Neuroinflammation

Neurol Neuroimmunol Neuroinflamm. 2021 Oct 5;8(6):e1090. doi: 10.1212/NXI.0000000000001090. Print 2021 Nov.

Abstract

Background and objectives: To evaluate the usefulness of CSF and plasma neurofilament light (Nf-L) as a biomarker for human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM).

Methods: Nf-L, CXCL10, and neopterin were measured by ELISA in 83 CSF samples obtained from 49 individuals living with HTLV-1/2. Plasma Nf-L was also measured by single molecule array. Results were correlated with duration of disease, age, mobility, CSF cell counts, CSF protein, and HTLV-1 proviral load.

Results: Nf-L was detected in all CSF samples (median [range] = 575 [791.8-2,349] pg/mL) and positively correlated with markers of inflammation (CXCL10 (r = 0.733), neopterin (r = 0.499), cell count (r = 0.403), and protein levels (r = 0.693) in CSF; p < 0.0015). There was an inverse correlation between Nf-L and duration of disease (r = -0.584, p < 0.0001). Wheelchair-dependent patients had high concentrations of markers of inflammation and neuronal damage. Concentrations of CXCL10, neopterin, and Nf-L remained elevated in follow-up samples (mean follow-up 5.2 years). Nf-L in plasma correlated with concentration of Nf-L, neopterin, CXCL10, and protein in CSF.

Conclusions: Nf-L in plasma and CSF has potential to be used as a biomarker of disease activity in HAM. Neuronal damage seems to be more intense early in disease but persists long term. Wheelchair-dependent patients have ongoing neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / cerebrospinal fluid
  • Female
  • Follow-Up Studies
  • HTLV-I Infections / blood
  • HTLV-I Infections / cerebrospinal fluid
  • HTLV-I Infections / diagnosis*
  • Humans
  • Male
  • Middle Aged
  • Neopterin / blood
  • Neopterin / cerebrospinal fluid
  • Neurofilament Proteins / blood*
  • Neurofilament Proteins / cerebrospinal fluid*
  • Neuroinflammatory Diseases / blood*
  • Neuroinflammatory Diseases / cerebrospinal fluid*
  • Neuroinflammatory Diseases / pathology
  • Neuroinflammatory Diseases / physiopathology
  • Spinal Cord Diseases / blood
  • Spinal Cord Diseases / cerebrospinal fluid
  • Spinal Cord Diseases / diagnosis*

Substances

  • Biomarkers
  • Chemokine CXCL10
  • Neurofilament Proteins
  • neurofilament protein L
  • Neopterin