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CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection

OBJECTIVE: To explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection. METHODS: In this retrospective cross-sectional study, we measured concentrations of the macrophage/microglial activation marker sTREM2 in CSF samples from 121 HIV-1–infected adults and 11 HIV-negati...

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Autores principales: Gisslén, Magnus, Heslegrave, Amanda, Veleva, Elena, Yilmaz, Aylin, Andersson, Lars-Magnus, Hagberg, Lars, Spudich, Serena, Fuchs, Dietmar, Price, Richard W., Zetterberg, Henrik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278890/
https://www.ncbi.nlm.nih.gov/pubmed/30568991
http://dx.doi.org/10.1212/NXI.0000000000000512
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author Gisslén, Magnus
Heslegrave, Amanda
Veleva, Elena
Yilmaz, Aylin
Andersson, Lars-Magnus
Hagberg, Lars
Spudich, Serena
Fuchs, Dietmar
Price, Richard W.
Zetterberg, Henrik
author_facet Gisslén, Magnus
Heslegrave, Amanda
Veleva, Elena
Yilmaz, Aylin
Andersson, Lars-Magnus
Hagberg, Lars
Spudich, Serena
Fuchs, Dietmar
Price, Richard W.
Zetterberg, Henrik
author_sort Gisslén, Magnus
collection PubMed
description OBJECTIVE: To explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection. METHODS: In this retrospective cross-sectional study, we measured concentrations of the macrophage/microglial activation marker sTREM2 in CSF samples from 121 HIV-1–infected adults and 11 HIV-negative controls and examined their correlations with other CSF and blood biomarkers of infection, inflammation, and neuronal injury. RESULTS: CSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD). In untreated HIV-1–infected patients without an HAD diagnosis, levels of CSF sTREM2 increased with decreasing CD4(+) T-cell counts. CSF concentrations of both sTREM2 and the neuronal injury marker neurofilament light protein (NFL) were significantly associated with age. CSF sTREM2 levels were also independently correlated with CSF NFL. Notably, this association was also observed in HIV-negative controls with normal CSF NFL. HIV-infected patients on suppressive antiretroviral treatment had CSF sTREM2 levels comparable to healthy controls. CONCLUSIONS: Elevations in CSF sTREM2 levels, an indicator of macrophage/microglial activation, are a common feature of untreated HIV-1 infection that increases with CD4(+) T-cell loss and reaches highest levels in HAD. The strong and independent association between CSF sTREM2 and CSF NFL suggests a linkage between microglial activation and neuronal injury in HIV-1 infection. CSF sTREM2 has the potential of being a useful biomarker of innate CNS immune activation in different stages of untreated and treated HIV-1 infection.
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spelling pubmed-62788902018-12-19 CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection Gisslén, Magnus Heslegrave, Amanda Veleva, Elena Yilmaz, Aylin Andersson, Lars-Magnus Hagberg, Lars Spudich, Serena Fuchs, Dietmar Price, Richard W. Zetterberg, Henrik Neurol Neuroimmunol Neuroinflamm Article OBJECTIVE: To explore changes in CSF sTREM2 concentrations in the evolving course of HIV-1 infection. METHODS: In this retrospective cross-sectional study, we measured concentrations of the macrophage/microglial activation marker sTREM2 in CSF samples from 121 HIV-1–infected adults and 11 HIV-negative controls and examined their correlations with other CSF and blood biomarkers of infection, inflammation, and neuronal injury. RESULTS: CSF sTREM2 increased with systemic and CNS HIV-1 disease severity, with the highest levels found in patients with HIV-associated dementia (HAD). In untreated HIV-1–infected patients without an HAD diagnosis, levels of CSF sTREM2 increased with decreasing CD4(+) T-cell counts. CSF concentrations of both sTREM2 and the neuronal injury marker neurofilament light protein (NFL) were significantly associated with age. CSF sTREM2 levels were also independently correlated with CSF NFL. Notably, this association was also observed in HIV-negative controls with normal CSF NFL. HIV-infected patients on suppressive antiretroviral treatment had CSF sTREM2 levels comparable to healthy controls. CONCLUSIONS: Elevations in CSF sTREM2 levels, an indicator of macrophage/microglial activation, are a common feature of untreated HIV-1 infection that increases with CD4(+) T-cell loss and reaches highest levels in HAD. The strong and independent association between CSF sTREM2 and CSF NFL suggests a linkage between microglial activation and neuronal injury in HIV-1 infection. CSF sTREM2 has the potential of being a useful biomarker of innate CNS immune activation in different stages of untreated and treated HIV-1 infection. Lippincott Williams & Wilkins 2018-11-07 /pmc/articles/PMC6278890/ /pubmed/30568991 http://dx.doi.org/10.1212/NXI.0000000000000512 Text en Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Gisslén, Magnus
Heslegrave, Amanda
Veleva, Elena
Yilmaz, Aylin
Andersson, Lars-Magnus
Hagberg, Lars
Spudich, Serena
Fuchs, Dietmar
Price, Richard W.
Zetterberg, Henrik
CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
title CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
title_full CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
title_fullStr CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
title_full_unstemmed CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
title_short CSF concentrations of soluble TREM2 as a marker of microglial activation in HIV-1 infection
title_sort csf concentrations of soluble trem2 as a marker of microglial activation in hiv-1 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278890/
https://www.ncbi.nlm.nih.gov/pubmed/30568991
http://dx.doi.org/10.1212/NXI.0000000000000512
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