Authors:
Gresle MM, Liu Y, Dagley LF, Haartsen J, Pearson F, Purcell AW, ..., Lucas RM, et al.
Authors notes:
Journal of Neurology, Neurosurgery and Psychiatry.
Keywords:
phosphorylated neurofilament heavy chain (pNF-H), titre, biomarker, axonal injury, multiple sclerosis (MS), ELISA, Multiple Sclerosis Severity Score (MSSS).
Abstract:
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).
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.
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.
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.