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

• Published in: Journal of neurovirology Vol. 22; no. 6; pp. 715 - 724
• Main Authors: de Almeida, Sergio M., Rotta, Indianara, Jiang, Yanxin, Li, Xiao, Raboni, Sonia M., Ribeiro, Clea E., Smith, Davey, Potter, Michael, Vaida, Florin, Letendre, Scott, Ellis, Ronald J.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2016
• Subjects: Biomedical and Life Sciences; Biomedicine; Immunology; Infectious Diseases; Lentivirus; Neurology; Neurosciences; Retroviridae; Virology; HIV-1; Biomarkers; Inflammatory; HIV-associated neurocognitive disorders (HANDs); Cerebrospinal fluid (CSF); Subtype
• ISSN: 1355-0284; 1538-2443
• DOI: 10.1007/s13365-016-0437-4

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.