TY - JOUR
T1 - CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease
AU - Anderson, Albert M.
AU - Fennema-Notestine, Christine
AU - Umlauf, Anya
AU - Taylor, Michael J.
AU - Clifford, David B.
AU - Marra, Christina M.
AU - Collier, Ann C.
AU - Gelman, Benjamin B.
AU - McArthur, Justin C.
AU - McCutchan, J. Allen
AU - Simpson, David M.
AU - Morgello, Susan
AU - Grant, Igor
AU - Letendre, Scott L.
N1 - Funding Information:
This work was supported by awards from the National Institutes of Health for the CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) (N01 MH2205, HHSN271201000036C, and P30 MH62512). The views expressed in this article are those of the authors and do not reflect the official policy or position of the US Government. AMA is supported by NIH K23 MH095679 and SLL is supported by K24 MH097673.
Publisher Copyright:
© 2015, Journal of NeuroVirology, Inc.
PY - 2015/10/1
Y1 - 2015/10/1
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.
KW - Acquired immunodeficiency syndrome
KW - Biomarkers
KW - Cerebrospinal fluid
KW - HIV-associated neurocognitive disorder
KW - Human immunodeficiency virus
UR - http://www.scopus.com/inward/record.url?scp=84945437046&partnerID=8YFLogxK
U2 - 10.1007/s13365-015-0359-6
DO - 10.1007/s13365-015-0359-6
M3 - Article
C2 - 26069183
AN - SCOPUS:84945437046
SN - 1355-0284
VL - 21
SP - 559
EP - 567
JO - Journal of NeuroVirology
JF - Journal of NeuroVirology
IS - 5
ER -