Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients

Gresle, Melissa; Liu, Y; Dagley, Laura F.; Haartsen, Jodi; Pearson, Francesca; Purcell, Anthony W.; Laverick, Louise; Petzold, Axel; Lucas, Robyn; Walt, Anneke van der; Prime, Hillary; Morris, Daniel C.; Taylor, BV; Shaw, Gerry; Butzkueven, Helmut

doi:10.1136/jnnp-2013-306789

Cited by 45 publications

(35 citation statements)

References 18 publications

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“…After CNS injury, pNfH is released into the extracellular fluid from where it diffuses into the CSF and finally enters the blood stream via the arachnoid villi. We have previously shown that pNfH levels are elevated after stroke [9] and others have found that pNfH levels are elevated in multiple sclerosis [30] which indicates that pNfH can enter the blood after CNS damage in humans. After degeneration of peripheral axons, we expect that pNfH could readily enter the blood stream.…”

Section: Discussionmentioning

confidence: 97%

Serial measurements of phosphorylated neurofilament-heavy in the serum of subjects with amyotrophic lateral sclerosis

McCombe

Pfluger

Singh

et al. 2015

Journal of the Neurological Sciences

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There is a need for a blood biomarker of disease activity in ALS. This marker needs to measure the loss of motor neurones. Phosphorylated neurofilament heavy chain (pNfH) in the serum is a biomarker of axonal injury. Previous studies have found that levels of pNfH are elevated in ALS. We have performed a serial study of pNfH levels in 98 subjects from our ALS clinic. There was significant elevation of levels of pNfH in subjects with ALS compared to controls, although there was considerable variability. In studies of individuals who had two or more serial samples, we found that the levels of pNfH increased over time in the early stage of disease. Levels were low in subjects with long survival. The rate of rise of pNfH was inversely correlated with survival. We suggest that the initial level of pNfH is a marker of disease severity and that changes in pNfH levels are markers of disease progression.

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Section: Discussionmentioning

confidence: 97%

Serial measurements of phosphorylated neurofilament-heavy in the serum of subjects with amyotrophic lateral sclerosis

McCombe

Pfluger

Singh

et al. 2015

Journal of the Neurological Sciences

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“…that IgM antibodies could arise through the mechanism of molecular 210 mimicry. The biological basis of a humoral response to α-glucose anti- 211 gen is still unclear, but it is of interest that this particular carbohydrate 212 (α-glucose) is found within the type IV collagen matrix of the BBB.…”

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confidence: 98%

Peripheral blood biomarkers in multiple sclerosis

D’Ambrosio

Pontecorvo

Colasanti

et al. 2015

Autoimmunity Reviews

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Multiple sclerosis is the most common autoimmune disorder affecting the central nervous system. The heterogeneity of pathophysiological processes in MS contributes to the highly variable course of the disease and unpredictable response to therapies. The major focus of the research on MS is the identification of biomarkers in biological fluids, such as cerebrospinal fluid or blood, to guide patient management reliably. Because of the difficulties in obtaining spinal fluid samples and the necessity for lumbar puncture to make a diagnosis has reduced, the research of blood-based biomarkers may provide increasingly important tools for clinical practice. However, currently there are no clearly established MS blood-based biomarkers. The availability of reliable biomarkers could radically alter the management of MS at critical phases of the disease spectrum, allowing for intervention strategies that may prevent evolution to long-term neurological disability. This article provides an overview of this research field and focuses on recent advances in blood-based biomarker research.

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“…The pNF-H level is associated with the severity of spinal cord injury (18) and may have adequate sensitivity to serve as a biomarker of treatment efficacy in patients with spinal cord injury (19). Increased pNF-H levels are also observed in patients with supraspinal CNS damage, such as that caused by multiple sclerosis (20), febrile seizures (21), hypoxic-ischemic encephalopathy (22), acute intracerebral hemorrhage, and other conditions. Thus, pNF-H has potential as an effective biomarker of CNS damage caused by either neuronal or axonal injury.…”

Section: Introductionmentioning

confidence: 99%

Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment

Natori

Ogata

Sumitani

et al. 2015

Clinical Cancer Research

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Purpose: Chemotherapy-induced cognitive impairment (CICI) is a clinically significant problem. Previous studies using magnetic resonance imaging indicated structural changes in the cerebral white matter of patients with CICI. Phosphorylated neurofilament heavy subunit (pNF-H), a major structural protein in axons, was recently reported to be elevated in the serum of patients with some central nervous system disorders. We performed a cross-sectional analysis of neuropsychological test results and serum pNF-H levels in patients undergoing adjuvant chemotherapy for breast cancer. Our hypothesis was that CICI is accompanied by axonal damage that can be detected by elevated serum pNF-H levels. Experimental Design: Seventy-six patients with early breast cancer in various phases of treatment (naïve to chemotherapy; after one, three, or seven cycles of chemotherapy; or with a history of chemotherapy) were assessed by self-administered neuropsychological tests and a single pNF-H measurement. The χ2 and Mann–Whitney tests were used for statistical analysis. Results: Increased pNF-H levels were observed in 28.8% of the patients who underwent chemotherapy, but in none of the chemotherapy-naïve patients or patients with a history of chemotherapy. The pNF-H–positive rate increased significantly in proportion to the number of chemotherapy cycles (one cycle, 5.0%; three cycles, 31.6%; seven cycles, 55.0%; P < 0.05). No significant differences in neuropsychological test results were observed among the groups. Conclusions: The serum pNF-H level in patients undergoing chemotherapy for breast cancer increased in a cumulative dose-dependent manner, suggesting its potential application as a biomarker of neural damage after chemotherapy. Clin Cancer Res; 21(6); 1348–52. ©2015 AACR.

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Serum phosphorylated neurofilament-heavy chain levels in multiple sclerosis patients

Abstract: 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.

Cited by 45 publications

References 18 publications

Serial measurements of phosphorylated neurofilament-heavy in the serum of subjects with amyotrophic lateral sclerosis

Serial measurements of phosphorylated neurofilament-heavy in the serum of subjects with amyotrophic lateral sclerosis

Peripheral blood biomarkers in multiple sclerosis

Potential Role of pNF-H, a Biomarker of Axonal Damage in the Central Nervous System, as a Predictive Marker of Chemotherapy-Induced Cognitive Impairment

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