title: A comparative study of CSF neurofilament light and heavy chain protein in MS.
abstract: BACKGROUND
  There is a lack of reliable biomarkers of axonal degeneration. Neurofilaments are promising candidates to fulfil this task. We compared two highly sensitive assays to measure two subunits of the neurofilament protein (neurofilament light (NfL) and neurofilament heavy chain (NfH)).
  
  
  METHODS
  We evaluated the analytical and clinical performance of the UmanDiagnostics NF-light(®) enzyme-linked immunosorbent assay (ELISA) in the cerebrospinal fluid (CSF) of a group of 148 patients with clinically isolated syndrome (CIS) or multiple sclerosis (MS), and 72 controls. We compared our results with referring levels of our previously-developed CSF NfH(SMI35) assay.
  
  
  RESULTS
  Exposure to room temperature (up to 8 days) or repetitive thawing (up to 4 thaws) did not influence measurement of NfL concentrations. Values of NfL were higher in all disease stages of CIS/MS, in comparison to controls (p ≤ 0.001). NfL levels correlated with the Expanded Disability Status Scale (EDSS) score in patients with relapsing disease (r(s) = 0.31; p = 0.002), spinal cord relapses and with CSF markers of acute inflammation. The ability of NfL to distinguish patients from controls was greater than that of NfH(SMI35) in both CIS patients (p = 0.001) and all MS stages grouped together (p = 0.035).
  
  
  CONCLUSIONS
  NfL proved to be a stable protein, an important prerequisite for a reliable biomarker, and the NF-light(®) ELISA performed better in discriminating patients from controls, compared with the ECL-NfH(SMI35) immunoassay. We confirmed and expanded upon previous findings regarding neurofilaments as quantitative markers of neurodegeneration. Our results further support the role of neurofilaments as a potential surrogate measure for neuroprotective treatment in MS studies.
authors.affiliation: Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, UK.
authors.forename: Jens
authors.initials: J
authors.lastname: Kuhle
authors.forename: Kim
authors.initials: K
authors.lastname: Plattner
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bestwick
authors.forename: Raija L
authors.initials: RL
authors.lastname: Lindberg
authors.forename: Sreeram V
authors.initials: SV
authors.lastname: Ramagopalan
authors.forename: Niklas
authors.initials: N
authors.lastname: Norgren
authors.forename: Ahuva
authors.initials: A
authors.lastname: Nissim
authors.forename: Andrea
authors.initials: A
authors.lastname: Malaspina
authors.forename: David
authors.initials: D
authors.lastname: Leppert
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000134:cerebrospinal fluid; D004185:Disability Evaluation; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007118:Immunoassay; D007249:Inflammation / Q000134:cerebrospinal fluid / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000473:pathology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D012372:ROC Curve; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins
keywords: Cerebrospinal fluid; biomarker; clinically isolated syndrome; disability; immunoassay; multiple sclerosis; neurodegeneration; neurofilament; neurofilament heavy chain; neurofilament light chain; relapse; study design