Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May 15:366:577845.
doi: 10.1016/j.jneuroim.2022.577845. Epub 2022 Mar 12.

Soluble CD14 is subtype-dependent in serum but not in cerebrospinal fluid in people with HIV

Sergio Monteiro de Almeida  1 , Bin Tang  2 , Florin Vaida  3 , Scott Letendre  4 , Ronald J Ellis  5 ; HNRC Group  6
Affiliations

Soluble CD14 is subtype-dependent in serum but not in cerebrospinal fluid in people with HIV

Sergio Monteiro de Almeida et al. J Neuroimmunol. .

Abstract

Monocytes and macrophages activation are crucial in human immunodeficiency virus (HIV) central nervous system (CNS) infection and HIV associated neurocognitive disorders (HAND) pathogenesis. The soluble form of CD14 (sCD14) is a marker of monocyte activation. We hypothesized that sCD14 levels would be lower in people with HIV-1 subtype C (HIV-1C) than in HIV-1B owing to a variant Tat cysteine dimotif (C30S31) with reduced chemotactic activity. A total of 68 paired cerebrospinal fluid (CSF) and blood samples from people with HIV (PWH); 27 samples of the HIV-1B subtype and 40 of the non-B HIV-1 subtypes (including 26,HIV-1C), and 18 HIV-negative controls were included. sCD14 levels were quantified using a high-sensitivity enzyme-linked immunosorbent assay. sCD14 increase in serum, but not in CSF, was higher in samples from HIV-1B than HIV-1C (p = 0.002; Cohen's d, 0.7). CSF or serum sCD14 values were not correlated with global deficit score or specific cognitive domains. The impact of HIV-1 on monocyte stimulation biomarkers evaluated by sCD14 in serum was subtype-dependent, higher in HIV-1B than HIV-1C, consistent with reduced chemotactic activity as hypothesized.

Keywords: Cerebrospinal fluid; HIV-1; HIV-associated neurocognitive disorders; Soluble CD14; Subtypes.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest and Source of Funding

The authors declare that there are no conflicts of interest regarding the publication of this article.

This research was supported by NIH R21 MH76651 (principal investigators: R. Ellis and S. de Almeida) and CFAR International Pilot Grant P30 AI036214 (principal investigator: S. de Almeida). Funding organizations did not contribute to the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Statistical analysis was performed by Bin Tang and Prof. Florin Vaida.

Declaration of Competing Interest

The authors declare that there are no conflicts of interest regarding the publication of this article.

Figures

Fig. 1.
Fig. 1.
Serum soluble CD14 in HIV1-B and HIV1-C samples. Boxes show the medians and interquartile ranges, and whiskers indicate the maximum and minimum values. The dots indicate the number of individuals in each group. Red dashed line represents serum soluble CD14 reference values, calculated in PWoH control group, mean ± 2 standard deviation. The comparison of all PWH versus PWoH (Ctrl), p < 0.001.
Fig. 2.
Fig. 2.
Correlation of sCD14 with blood CSF barrier dysfunction biomarkers and current peripheral blood CD4 count. Correlation coefficients (ρ) were estimated using Spearman’s rank-order method, after the exclusion of the outlier’s values; results were shown in ρ (95% confidence interval [CI]). Q sCD14 = CSF/serum sCD14; Q Alb = CSF/serum albumin.
Fig. 3.
Fig. 3.
Correlations of sCD14 in CSF and serum with inflammatory biomarkers, β2m, neopterin, and CCL-2. Correlation coefficients (ρ) were estimated using Spearman’s rank-order method, after the exclusion of the outlier’s values; results were shown in ρ (95% confidence interval [CI]). Q sCD14 = CSF/serum sCD14; Q Alb = CSF/serum albumin.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Albini A, Benelli R, Giunciuglio D, Cai T, Mariani G, Ferrini S, Noonan DM, 1998. Identification of a novel domain of HIV tat involved in monocyte chemotaxis. J. Biol. Chem. 273, 15895–15900. - PubMed
    1. Ancuta P, Kamat A, Kunstman KJ, Kim E-Y, Autissier P, Wurcel A, Zaman T, Stone D, Mefford M, Morgello S, Singer EJ, Wolinsky SM, Gabuzda D, 2008. Microbial translocation is associated with increased monocyte activation and dementia in aids patients. PLoS One 3 (6), e2516. 10.1371/journal.pone.0002516. - DOI - PMC - PubMed
    1. Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE, 2007. Updated research nosology for HIV-associated neurocognitive disorders. Neurology 69, 1789–1799. - PMC - PubMed
    1. Beall CJ, Mahajan S, Kuhn DE, Kolattukudy PE, 1996. Site-directed mutagenesis of monocyte chemoattractant protein-1 identifies two regions of the polypeptide essential for biological activity. Biochem. J. 313, 633–640. - PMC - PubMed
    1. Becher B, Fedorowicz V, Antel JP, 1996. Regulation of CD14 expression on human adult central nervous system-derived microglia. J. Neurosci. Res. 45, 375–381. - PubMed