Biomarkers of chemotaxis and inflammation in cerebrospinal fluid and serum in individuals with HIV-1 subtype C versus B.

Abstract

A defective chemokine motif in the HIV-1 Tat protein has been hypothesized to alter central nervous system cellular trafficking and inflammation, rendering HIV-1 subtype C less neuropathogenic than B. To evaluate this hypothesis, we compared biomarkers of cellular chemotaxis and inflammation in cerebrospinal fluid (CSF) and serum in individuals infected with HIV-1 subtypes B (n = 27) and C (n = 25) from Curitiba, Brazil. None had opportunistic infections. Chemokines (MCP-1, MIP-1α, MIP-1β, RANTES, IP-10) and cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-10) were measured using the multiplex bead suspension array immunoassays or ELISA HD. CSF and serum biomarker concentrations were compared between subtype B and C groups and HIV-positive and HIV-negative subjects (N = 19) using an independent group t test (unadjusted analysis) and linear regression (adjusted analysis), controlling for nadir CD4 and CSF and plasma HIV RNA suppression. CSF levels of cytokines and chemokines were significantly (p < 0.05) elevated in HIV-positive versus HIV-negative participants for 7/13 biomarkers measured, but levels did not differ for subtypes B and C. Serum levels were significantly elevated for 4/13 markers, with no significant differences between subtypes B and C. Although pleocytosis was much more frequent in HIV-positive than in HIV-negative individuals (27 vs. 0 %), subtypes B and C did not differ (32 and 22 %; p = 0.23). We did not find molecular evidence to support the hypothesis that intrathecal chemotaxis and inflammation is less in HIV-1 subtype C than in subtype B. Biomarker changes in CSF were more robust than in serum, suggesting compartmentalization of the immunological response to HIV.

• Authors: Sergio M de Almeida, Indianara Rotta, Yanxin Jiang, Xiao Li, Sonia M Raboni, Clea E Ribeiro, Davey Smith, Michael Potter, Florin Vaida, Scott Letendre, Ronald J Ellis, HNRC Group
• Journal: Journal of neurovirology (J Neurovirol) Vol. 22 Issue 6 Pg. 715-724 (12 2016) ISSN: 1538-2443 [Electronic] United States
• PMID: 27400932 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Chemokines, CC
• Interleukins
• RNA, Viral
• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Adult
• Biomarkers (blood, cerebrospinal fluid)
• CD4-Positive T-Lymphocytes (immunology, metabolism, virology)
• Case-Control Studies
• Central Nervous System (immunology, metabolism, virology)
• Chemokines, CC (blood, cerebrospinal fluid)
• Chemotaxis (immunology)
• Female
• HIV Infections (blood, cerebrospinal fluid, immunology, virology)
• HIV-1 (classification, immunology, pathogenicity)
• Humans
• Interferon-gamma (blood, cerebrospinal fluid)
• Interleukins (blood, cerebrospinal fluid)
• Leukocytosis (blood, cerebrospinal fluid, immunology, virology)
• Linear Models
• Male
• Middle Aged
• Molecular Typing
• RNA, Viral (immunology)
• Tumor Necrosis Factor-alpha (blood, cerebrospinal fluid)
• Viral Load (immunology)