CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease

Albert M. Anderson, Christine Fennema-Notestine, Anya Umlauf, Michael J. Taylor, David B. Clifford, Christina M. Marra, Ann C. Collier, Benjamin Gelman, Justin C. McArthur, J. Allen McCutchan, David M. Simpson, Susan Morgello, Igor Grant, Scott L. Letendre

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R2 0.179, p <0.001) as well as MCP-1 and MI in FWM (R2 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 (R2 0. 075, p = 0.01) and IP-10 (R2 0.106, p = 0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM (R2 0.224, p <0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals.

Original languageEnglish (US)
Pages (from-to)559-567
Number of pages9
JournalJournal of NeuroVirology
Volume21
Issue number5
DOIs
StatePublished - Jun 12 2015

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Creatine
Virus Diseases
Chemotaxis
Chemokine CCL2
Cerebrospinal Fluid
Monocytes
Magnetic Resonance Spectroscopy
Biomarkers
HIV
Choline
Basal Ganglia
Inositol
Chemokine CXCL10
Chemokine CXCL12
Macrophage Activation
Brain
Therapeutics
Linear Models
Intercellular Signaling Peptides and Proteins
Cross-Sectional Studies

Keywords

  • Acquired immunodeficiency syndrome
  • Biomarkers
  • Cerebrospinal fluid
  • HIV-associated neurocognitive disorder
  • Human immunodeficiency virus

ASJC Scopus subject areas

  • Virology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Neurology

Cite this

Anderson, A. M., Fennema-Notestine, C., Umlauf, A., Taylor, M. J., Clifford, D. B., Marra, C. M., ... Letendre, S. L. (2015). CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease. Journal of NeuroVirology, 21(5), 559-567. https://doi.org/10.1007/s13365-015-0359-6

CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease. / Anderson, Albert M.; Fennema-Notestine, Christine; Umlauf, Anya; Taylor, Michael J.; Clifford, David B.; Marra, Christina M.; Collier, Ann C.; Gelman, Benjamin; McArthur, Justin C.; McCutchan, J. Allen; Simpson, David M.; Morgello, Susan; Grant, Igor; Letendre, Scott L.

In: Journal of NeuroVirology, Vol. 21, No. 5, 12.06.2015, p. 559-567.

Research output: Contribution to journalArticle

Anderson, AM, Fennema-Notestine, C, Umlauf, A, Taylor, MJ, Clifford, DB, Marra, CM, Collier, AC, Gelman, B, McArthur, JC, McCutchan, JA, Simpson, DM, Morgello, S, Grant, I & Letendre, SL 2015, 'CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease', Journal of NeuroVirology, vol. 21, no. 5, pp. 559-567. https://doi.org/10.1007/s13365-015-0359-6
Anderson, Albert M. ; Fennema-Notestine, Christine ; Umlauf, Anya ; Taylor, Michael J. ; Clifford, David B. ; Marra, Christina M. ; Collier, Ann C. ; Gelman, Benjamin ; McArthur, Justin C. ; McCutchan, J. Allen ; Simpson, David M. ; Morgello, Susan ; Grant, Igor ; Letendre, Scott L. / CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease. In: Journal of NeuroVirology. 2015 ; Vol. 21, No. 5. pp. 559-567.
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abstract = "Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 {\%} on cART and 37 {\%} with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R2 0.179, p <0.001) as well as MCP-1 and MI in FWM (R2 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 (R2 0. 075, p = 0.01) and IP-10 (R2 0.106, p = 0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM (R2 0.224, p <0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals.",
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AU - Fennema-Notestine, Christine

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AU - Clifford, David B.

AU - Marra, Christina M.

AU - Collier, Ann C.

AU - Gelman, Benjamin

AU - McArthur, Justin C.

AU - McCutchan, J. Allen

AU - Simpson, David M.

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AU - Grant, Igor

AU - Letendre, Scott L.

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N2 - Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R2 0.179, p <0.001) as well as MCP-1 and MI in FWM (R2 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 (R2 0. 075, p = 0.01) and IP-10 (R2 0.106, p = 0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM (R2 0.224, p <0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals.

AB - Human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART), supporting the need to better understand HIV neuropathogenesis. Magnetic resonance spectroscopy (MRS) of the brain has demonstrated abnormalities in HIV-infected individuals despite cART. We examined the associations between MRS metabolites and selected cerebrospinal fluid (CSF) biomarkers reflecting monocyte/macrophage activation and chemotaxis. A multicenter cross-sectional study involving five sites in the USA was conducted. The following CSF biomarkers were measured: soluble CD14 (sCD14), monocyte chemotactic protein-1 (MCP-1), interferon inducible protein 10 (IP-10), and stromal cell-derived growth factor 1 alpha (SDF-1α). The following MRS metabolites were measured from basal ganglia (BG), frontal white matter (FWM), and frontal gray matter (FGM): N-acetylaspartate (NAA), myo-inositol (MI), choline (Cho), and creatine (Cr). CSF biomarkers were compared to absolute MRS metabolites as well as metabolite/Cr ratios using linear regression. Eighty-three HIV-infected individuals were included, 78 % on cART and 37 % with HAND. The most robust positive correlations were between MCP-1 and Cho in BG (R2 0.179, p <0.001) as well as MCP-1 and MI in FWM (R2 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 (R2 0. 075, p = 0.01) and IP-10 (R2 0.106, p = 0.003). Comparing biomarkers to MRS metabolite/Cr ratios impacted some relationships, e.g., higher sCD14 levels were associated with lower Cho/Cr ratios in FGM (R2 0.224, p <0.001), although higher MCP-1 levels remained associated with Cho/Cr in BG. These findings provide evidence that monocyte activation and chemotaxis continue to contribute to HIV-associated brain abnormalities in cART-treated individuals.

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