Biomarkers of chemotaxis and inflammation in cerebrospinal fluid and serum in individuals with HIV-1 subtype C versus B |
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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 The HNRC Group |
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Institution: | 1.Universidade Federal do Paraná,Curitiba,Brazil;2.Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil,Instituto de Pesquisa Pelé Pequeno Príncipe,Curitiba,Brazil;3.Se??o de Virologia, Setor Análises Clínicas,Hospital de Clínicas – UFPR,Curitiba,Brazil;4.Alzheimer’s Therapeutic Research Institute,University of Southern California,San Diego,USA;5.Chicago Cleaning House,Chicago,USA;6.Division of Infectious Diseases, Department of Medicine,University of California,San Diego,USA;7.HIV Neurobehavioral Research Center,University of California, San Diego,San Diego,USA;8.Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health,University of California,San Diego,USA;9.Department of Neurosciences,University of California,San Diego,USA |
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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. |
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