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Research paper
Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients
  1. M M Gresle1,2,
  2. Y Liu3,
  3. L F Dagley4,
  4. J Haartsen5,
  5. F Pearson5,
  6. A W Purcell4,6,
  7. L Laverick1,
  8. A Petzold7,
  9. R M Lucas8,
  10. A Van der Walt2,
  11. H Prime5,9,
  12. D R Morris1,
  13. B V Taylor10
  14. on behalf of the Ausimmune Consortium
  1. G Shaw11,12,
  2. H Butzkueven1,2,5
  1. 1The Department of Medicine, University of Melbourne, Parkville, Victoria, Australia
  2. 2Melbourne Brain Centre, Royal Melbourne Hospital, Parkville, Victoria, Australia
  3. 3Department of Radiology, Xuanwu Hospital Capital Medical University, Beijing, China
  4. 4Bio21 Institute, University of Melbourne, Parkville, Victoria, Australia
  5. 5Eastern Clinical Research Unit Box-Hill Hospital, Victoria, Australia
  6. 6Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia
  7. 7Department of Neuroimmunology, UCL institute of Neurology, London, UK
  8. 8National Centre for Epidemiology and Population Health, College of Medicine, Biology and Environment, Australian National University, Canberra, Australian Capital Territory, Australia
  9. 9MRI services, MIA, Box Hill, Victoria, Australia
  10. 10The Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia
  11. 11Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida, USA
  12. 12EnCor Biotechnology Inc. Gainesville, Florida
  1. Correspondence to Dr Melissa Gresle, Department of Medicine, University of Melbourne, 4th Floor Clinical Sciences Building, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; mgresle{at}


Objectives 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.


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