Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients

Melissa M Gresle, Y Liu, Laura F Dagley, Jodi Haartsen, Felicity Pearson, Anthony W Purcell, Louise Laverick, Axel Petzold, Robyn M Lucas, Anneke van der Walt, Hayden Prime, Kelli-Jane L Lazarus, Bruce V Taylor, D R Morris, Gerry P J Shaw, Helmut Butzkueven

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19 Citations (Scopus)

Abstract

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 resampled 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.

Original languageEnglish
Pages (from-to)1209-1213
Number of pages5
JournalJournal of Neurology, Neurosurgery and Psychiatry
Volume85
Issue number11
DOIs
Publication statusPublished - 1 Nov 2014

Cite this

Gresle, Melissa M ; Liu, Y ; Dagley, Laura F ; Haartsen, Jodi ; Pearson, Felicity ; Purcell, Anthony W ; Laverick, Louise ; Petzold, Axel ; Lucas, Robyn M ; van der Walt, Anneke ; Prime, Hayden ; Lazarus, Kelli-Jane L ; Taylor, Bruce V ; Morris, D R ; Shaw, Gerry P J ; Butzkueven, Helmut. / Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients. In: Journal of Neurology, Neurosurgery and Psychiatry. 2014 ; Vol. 85, No. 11. pp. 1209-1213.
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abstract = "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 resampled 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.",
author = "Gresle, {Melissa M} and Y Liu and Dagley, {Laura F} and Jodi Haartsen and Felicity Pearson and Purcell, {Anthony W} and Louise Laverick and Axel Petzold and Lucas, {Robyn M} and {van der Walt}, Anneke and Hayden Prime and Lazarus, {Kelli-Jane L} and Taylor, {Bruce V} and Morris, {D R} and Shaw, {Gerry P J} and Helmut Butzkueven",
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Gresle, MM, Liu, Y, Dagley, LF, Haartsen, J, Pearson, F, Purcell, AW, Laverick, L, Petzold, A, Lucas, RM, van der Walt, A, Prime, H, Lazarus, K-JL, Taylor, BV, Morris, DR, Shaw, GPJ & Butzkueven, H 2014, 'Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients', Journal of Neurology, Neurosurgery and Psychiatry, vol. 85, no. 11, pp. 1209-1213. https://doi.org/10.1136/jnnp-2013-306789

Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients. / Gresle, Melissa M; Liu, Y; Dagley, Laura F; Haartsen, Jodi; Pearson, Felicity; Purcell, Anthony W; Laverick, Louise; Petzold, Axel; Lucas, Robyn M; van der Walt, Anneke; Prime, Hayden; Lazarus, Kelli-Jane L; Taylor, Bruce V; Morris, D R; Shaw, Gerry P J; Butzkueven, Helmut.

In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 85, No. 11, 01.11.2014, p. 1209-1213.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients

AU - Gresle, Melissa M

AU - Liu, Y

AU - Dagley, Laura F

AU - Haartsen, Jodi

AU - Pearson, Felicity

AU - Purcell, Anthony W

AU - Laverick, Louise

AU - Petzold, Axel

AU - Lucas, Robyn M

AU - van der Walt, Anneke

AU - Prime, Hayden

AU - Lazarus, Kelli-Jane L

AU - Taylor, Bruce V

AU - Morris, D R

AU - Shaw, Gerry P J

AU - Butzkueven, Helmut

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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 resampled 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.

AB - 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 resampled 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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U2 - 10.1136/jnnp-2013-306789

DO - 10.1136/jnnp-2013-306789

M3 - Article

VL - 85

SP - 1209

EP - 1213

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

SN - 0022-3050

IS - 11

ER -