title: Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients.
abstract: OBJECTIVE
  We evaluated whether the measurement of serum phosphorylated neurofilament heavy chain (pNF-H) titre is likely to be a valid biomarker of axonal injury in multiple sclerosis (MS).
  
  
  METHODS
  Serum pNF-H concentrations were measured by ELISA in cases with relapsing-remitting (RR)-MS (n=81), secondary progressive (SP) MS (n=13) and primary progressive (PP)-MS; n=6) MS; first demyelinating event (FDE; n=82); and unaffected controls (n=135). A subset of MS cases (n=45) were re-sampled on one or multiple occasions. The Multiple Sclerosis Severity Score (MSSS) and MRI measures were used to evaluate associations between serum pNF-H status, disease severity and cerebral lesion load and activity.
  
  
  RESULTS
  We confirmed the presence of pNF-H peptides in serum by ELISA. We showed that a high serum pNF-H titre was detectable in 9% of RR-MS and FDE cases, and 38.5% of SP-MS cases. Patients with a high serum pNF-H titre had higher average MSSS scores and T2 lesion volumes than patients with a low serum pNF-H titre. Repeated sampling of a subset of MS cases showed that pNF-H levels can fluctuate over time, likely reflecting temporal dynamics of axonal injury in MS.
  
  
  CONCLUSIONS
  A subset of FDE/MS cases was found to have a high serum pNF-H titre, and this was associated with changes in clinical outcome measures. We propose that routine measurement of serum pNF-H should be further investigated for monitoring axonal injury in MS.
authors.affiliation: The Department of Medicine, University of Melbourne, Parkville, Victoria, Australia Melbourne Brain Centre, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: M M
authors.initials: MM
authors.lastname: Gresle
authors.affiliation: Department of Radiology, Xuanwu Hospital Capital Medical University, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: L F
authors.initials: LF
authors.lastname: Dagley
authors.affiliation: Eastern Clinical Research Unit Box-Hill Hospital, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Haartsen
authors.affiliation: Eastern Clinical Research Unit Box-Hill Hospital, Victoria, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Pearson
authors.affiliation: Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia.
authors.forename: A W
authors.initials: AW
authors.lastname: Purcell
authors.affiliation: The Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Laverick
authors.affiliation: Department of Neuroimmunology, UCL institute of Neurology, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Petzold
authors.affiliation: National Centre for Epidemiology and Population Health, College of Medicine, Biology and Environment, Australian National University, Canberra, Australian Capital Territory, Australia.
authors.forename: R M
authors.initials: RM
authors.lastname: Lucas
authors.affiliation: Melbourne Brain Centre, Royal Melbourne Hospital, Parkville, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Van der Walt
authors.affiliation: Eastern Clinical Research Unit Box-Hill Hospital, Victoria, Australia MRI services, MIA, Box Hill, Victoria, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Prime
authors.affiliation: The Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: D R
authors.initials: DR
authors.lastname: Morris
authors.affiliation: The Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.
authors.forename: B V
authors.initials: BV
authors.lastname: Taylor
authors.affiliation: Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA EnCor Biotechnology Inc. Gainesville, Florida.
authors.forename: G
authors.initials: G
authors.lastname: Shaw
authors.affiliation: The Department of Medicine, University of Melbourne, Parkville, Victoria, Australia Melbourne Brain Centre, Royal Melbourne Hospital, Parkville, Victoria, Australia Eastern Clinical Research Unit Box-Hill Hospital, Victoria, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000473:pathology; D020528:Multiple Sclerosis, Chronic Progressive / Q000097:blood / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000473:pathology; D016900:Neurofilament Proteins / Q000097:blood*; D059906:Neuroimaging; D010766:Phosphorylation; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D016900:Neurofilament Proteins; C051774:neurofilament protein H
keywords: MULTIPLE SCLEROSIS