CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease.
Title | CSF biomarkers of monocyte activation and chemotaxis correlate with magnetic resonance spectroscopy metabolites during chronic HIV disease. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Anderson, AM, Fennema-Notestine, C, Umlauf, A, Taylor, MJ, Clifford, DB, Marra, CM, Collier, AC, Gelman, BB, McArthur, JC, J McCutchan, A, Simpson, DM, Morgello, S, Grant, I, Letendre, SL |
Corporate Authors | CHARTER Group |
Journal | J Neurovirol |
Volume | 21 |
Issue | 5 |
Pagination | 559-67 |
Date Published | 2015 Oct |
ISSN | 1538-2443 |
Keywords | Adult, AIDS Dementia Complex, Biomarkers, Brain, CHARTER, Chemotaxis, Leukocyte, Cohort Studies, Cross-Sectional Studies, Female, Humans, Internal, Magnetic Resonance Spectroscopy, Male, Middle Aged, Monocytes |
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. |
DOI | 10.1007/s13365-015-0359-6 |
Alternate Journal | J Neurovirol |
PubMed ID | 26069183 |
PubMed Central ID | PMC5008689 |
Grant List | HHSN271201000036C / / PHS HHS / United States K24 MH097673 / MH / NIMH NIH HHS / United States P30 MH62512 / MH / NIMH NIH HHS / United States HHSN271201000036C / MH / NIMH NIH HHS / United States N01 MH2205 / MH / NIMH NIH HHS / United States HHSN271201000027C / MH / NIMH NIH HHS / United States P30 MH062512 / MH / NIMH NIH HHS / United States K23 MH095679 / MH / NIMH NIH HHS / United States |