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J Neurovirol. 2016 Dec;22(6):715-724. Epub 2016 Jul 11.

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

Author information

1
Universidade Federal do Paraná, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.
2
Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil. sergio.ma@ufpr.br.
3
Seção de Virologia, Setor Análises Clínicas, Hospital de Clínicas - UFPR, Rua Padre Camargo, 280, Curitiba, PR, Brazil, 80060-240. sergio.ma@ufpr.br.
4
Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
5
Faculdades Pequeno Príncipe, Curitiba, Paraná, Brazil, Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Paraná, Brazil.
6
Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego, CA, USA.
7
Chicago Cleaning House, Chicago, IL, USA.
8
Division of Infectious Diseases, Department of Medicine, University of California, San Diego, CA, USA.
9
HIV Neurobehavioral Research Center, University of California, San Diego, San Diego, CA, USA.
10
Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California, San Diego, CA, USA.
11
Department of Neurosciences, University of California, San Diego, CA, USA.

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.

KEYWORDS:

Biomarkers; Cerebrospinal fluid (CSF); HIV-1; HIV-associated neurocognitive disorders (HANDs); Inflammatory; Subtype

PMID:
27400932
PMCID:
PMC5130607
DOI:
10.1007/s13365-016-0437-4
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

SERGIO M. DE ALMEIDA , the author declare that have no conflict of interest. YANXIN JIANG , the author declare that have no conflict of interest. INDIANARA ROTTA, the author declare that have no conflict of interest. XIAO LI , the author declare that have no conflict of interest. SONIA M. RABONI , the author declare that have no conflict of interest. CLEA E. RIBEIRO , the author declare that have no conflict of interest. DAVEY SMITH , the author declare that have no conflict of interest. MICHAEL POTTER , the author declare that have no conflict of interest. FLORIN VAIDA , the author declare that have no conflict of interest. SCOTT LETENDRE , the author declare that have no conflict of interest. RONALD J. ELLIS , the author declare that have no conflict of interest.

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