title: 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.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.|Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.|Seção de Virologia, Setor Análises Clínicas, Hospital de Clínicas - UFPR, Rua Padre Camargo, 280, Curitiba, PR, Brazil, 80060-240. sergio.ma@ufpr.br.
authors.forename: Sergio M
authors.initials: SM
authors.lastname: de Almeida
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.|Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil.
authors.forename: Indianara
authors.initials: I
authors.lastname: Rotta
authors.affiliation: Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
authors.forename: Yanxin
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Chicago Cleaning House, Chicago, IL, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Raboni
authors.affiliation: Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Clea E
authors.initials: CE
authors.lastname: Ribeiro
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Diego, CA, USA.
authors.forename: Davey
authors.initials: D
authors.lastname: Smith
authors.affiliation: HIV Neurobehavioral Research Center, University of California, San Diego, San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Potter
authors.affiliation: Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California, San Diego, CA, USA.
authors.forename: Florin
authors.initials: F
authors.lastname: Vaida
authors.affiliation: Chicago Cleaning House, Chicago, IL, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Letendre
authors.affiliation: HIV Neurobehavioral Research Center, University of California, San Diego, San Diego, CA, USA.|Department of Neurosciences, University of California, San Diego, CA, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Ellis
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D016022:Case-Control Studies; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019742:Chemokines, CC / Q000097:blood / Q000134:cerebrospinal fluid*; D002633:Chemotaxis / Q000276:immunology*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000134:cerebrospinal fluid*; D007378:Interleukins / Q000097:blood / Q000134:cerebrospinal fluid*; D007964:Leukocytosis / Q000097:blood / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000821:virology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D012367:RNA, Viral / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000134:cerebrospinal fluid*; D019562:Viral Load / Q000276:immunology
chemical_list: D015415:Biomarkers; D019742:Chemokines, CC; D007378:Interleukins; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: Biomarkers; Cerebrospinal fluid (CSF); HIV-1; HIV-associated neurocognitive disorders (HANDs); Inflammatory; Subtype