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Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study

BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for...

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Autores principales: Gisslén, Magnus, Price, Richard W., Andreasson, Ulf, Norgren, Niklas, Nilsson, Staffan, Hagberg, Lars, Fuchs, Dietmar, Spudich, Serena, Blennow, Kaj, Zetterberg, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739412/
https://www.ncbi.nlm.nih.gov/pubmed/26870824
http://dx.doi.org/10.1016/j.ebiom.2015.11.036
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author Gisslén, Magnus
Price, Richard W.
Andreasson, Ulf
Norgren, Niklas
Nilsson, Staffan
Hagberg, Lars
Fuchs, Dietmar
Spudich, Serena
Blennow, Kaj
Zetterberg, Henrik
author_facet Gisslén, Magnus
Price, Richard W.
Andreasson, Ulf
Norgren, Niklas
Nilsson, Staffan
Hagberg, Lars
Fuchs, Dietmar
Spudich, Serena
Blennow, Kaj
Zetterberg, Henrik
author_sort Gisslén, Magnus
collection PubMed
description BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. METHODS: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. FINDINGS: Plasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4(+) T cells. INTERPRETATION: These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings.
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spelling pubmed-47394122016-02-11 Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study Gisslén, Magnus Price, Richard W. Andreasson, Ulf Norgren, Niklas Nilsson, Staffan Hagberg, Lars Fuchs, Dietmar Spudich, Serena Blennow, Kaj Zetterberg, Henrik EBioMedicine Research Paper BACKGROUND: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. METHODS: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. FINDINGS: Plasma and CSF NFL concentrations were very highly correlated (r = 0.89, P < 0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4(+) T cells. INTERPRETATION: These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings. Elsevier 2015-11-22 /pmc/articles/PMC4739412/ /pubmed/26870824 http://dx.doi.org/10.1016/j.ebiom.2015.11.036 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Gisslén, Magnus
Price, Richard W.
Andreasson, Ulf
Norgren, Niklas
Nilsson, Staffan
Hagberg, Lars
Fuchs, Dietmar
Spudich, Serena
Blennow, Kaj
Zetterberg, Henrik
Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
title Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
title_full Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
title_fullStr Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
title_full_unstemmed Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
title_short Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
title_sort plasma concentration of the neurofilament light protein (nfl) is a biomarker of cns injury in hiv infection: a cross-sectional study
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739412/
https://www.ncbi.nlm.nih.gov/pubmed/26870824
http://dx.doi.org/10.1016/j.ebiom.2015.11.036
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