Neurofilament light antibodies in serum reflect response to natalizumab treatment in multiple sclerosis

Mult Scler. 2014 Sep;20(10):1355-62. doi: 10.1177/1352458514521887. Epub 2014 Feb 10.

Abstract

Background: Increased levels of antibodies to neurofilament light protein (NF-L) in biological fluids have been found to reflect neuroinflammatory responses and neurodegeneration in multiple sclerosis (MS).

Objective: To evaluate whether levels of serum antibodies against NF-L correlate with clinical variants and treatment response in MS.

Methods: The autoantibody reactivity to NF-L protein was tested in serum samples from patients with relapsing-remitting MS (RRMS) (n=22) and secondary progressive MS (SPMS) (n=26). Two other cohorts of RRMS patients under treatment with natalizumab were analysed cross-sectionally (n=16) and longitudinally (n=24). The follow-up samples were taken at 6, 12, 18 and 24 months after treatment, and the NF-L antibody levels were compared against baseline levels.

Results: NF-L antibodies were higher in MS clinical groups than healthy controls and in RRMS compared to SPMS patients (p<0.001). NF-L antibody levels were lower in natalizumab treated than in untreated patients (p<0.001). In the longitudinal series, NF-L antibody levels decreased over time and a significant difference was found following 24 months of treatment compared with baseline measurements (p=0.001).

Conclusions: Drug efficacy in MS treatment indicates the potential use of monitoring the content of antibodies against the NF-L chain as a predictive biomarker of treatment response in MS.

Keywords: Neurofilament light chain; antibodies; multiple sclerosis; natalizumab treatment; neurodegeneration; neuroinflammation.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Autoantibodies / blood*
  • Biomarkers / blood
  • Case-Control Studies
  • Cross-Sectional Studies
  • Disability Evaluation
  • Drug Monitoring / methods
  • Enzyme-Linked Immunosorbent Assay
  • Europe
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / blood
  • Multiple Sclerosis, Chronic Progressive / diagnosis
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Chronic Progressive / immunology
  • Multiple Sclerosis, Relapsing-Remitting / blood
  • Multiple Sclerosis, Relapsing-Remitting / diagnosis
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Natalizumab
  • Neurofilament Proteins / immunology*
  • Predictive Value of Tests
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Autoantibodies
  • Biomarkers
  • Immunosuppressive Agents
  • Natalizumab
  • Neurofilament Proteins
  • neurofilament protein L