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Observational Study
. 2015 Oct;21(5):559-67.
doi: 10.1007/s13365-015-0359-6. Epub 2015 Jun 12.

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

Albert M Anderson  1 , Christine Fennema-Notestine  2   3 , Anya Umlauf  2   3 , Michael J Taylor  2   3 , David B Clifford  4 , Christina M Marra  5 , Ann C Collier  5 , Benjamin B Gelman  6 , Justin C McArthur  7 , J Allen McCutchan  2   3 , David M Simpson  8 , Susan Morgello  8 , Igor Grant  2   3 , Scott L Letendre  9   10 ; CHARTER Group
Collaborators, Affiliations
Observational Study

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

Albert M Anderson et al. J Neurovirol. 2015 Oct.

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 (R (2) 0.179, p < 0.001) as well as MCP-1 and MI in FWM (R (2) 0.137, p = 0.002). Higher Cr levels in FWM were associated with MCP-1 (R (2) 0. 075, p = 0.01) and IP-10 (R (2) 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 (R (2) 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.

Keywords: Acquired immunodeficiency syndrome; Biomarkers; Cerebrospinal fluid; HIV-associated neurocognitive disorder; Human immunodeficiency virus.

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Figures

Figure 1
Figure 1
Representative Axial T1 sections with MRS voxels: Frontal Gray (FGM) & White (FWM) Matter; and Basal Ganglia (BG).
Figure 2
Figure 2
Associations between selected CSF biomarkers and cerebral metabolites. Slopes, R-squared, and p-values were derived from multivariable models controlling for scanner, relevant imaging covariate, and significant medical covariates.
See this image and copyright information in PMC

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