Soluble CD14, CD163, and CD27 biomarkers distinguish ART-suppressed youth living with HIV from healthy controls.

TitleSoluble CD14, CD163, and CD27 biomarkers distinguish ART-suppressed youth living with HIV from healthy controls.
Publication TypePublication
Year of Publication2018
AuthorsWilliams JC, Zhang X, Karki M, Chi Y-Y, Wallet SM, Rudy BJ, Nichols SL, Goodenow MM, Sleasman JW
JournalJ Leukoc Biol
Volume103
Issue4
Pagination671-680
Date Published2018 04
ISSN1938-3673
KeywordsAdult, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Antiretroviral Therapy, Highly Active, Biomarkers, Case-Control Studies, Female, HIV, HIV Infections, Humans, Lipopolysaccharide Receptors, Longitudinal Studies, Lymphocyte Activation, Macrophage Activation, Male, Receptors, Cell Surface, Tumor Necrosis Factor Receptor Superfamily, Member 7, Viral Load, Young Adult
Abstract

<p><b>OBJECTIVE: </b>To define inflammatory pathways in youth living with HIV infection (YLWH), assessments of biomarkers associated with lymphocyte and macrophage activation, vascular injury, or bone metabolism were performed in YLWH in comparison with healthy controls (HC).</p><p><b>DESIGN: </b>Longitudinal multicenter study comparing biomarkers in YLWH suppressed on antiretroviral therapy (ART), those with ongoing viral replication, and HC were compared using single blood samples obtained at end of study.</p><p><b>METHODS: </b>Twenty-three plasma proteins were measured by ELISA or multiplex assays. Principal component analysis (PCA) was used to define contributions of individual biomarkers to define outcome groups.</p><p><b>RESULTS: </b>The study cohort included 129 predominantly African American, male participants, 21-25 years old at entry. Nine biomarkers of lymphocyte and macrophage activation and cardiovascular injury differed between HC and YLWH. Significant positive correlations were identified between lymphocyte and macrophage activation biomarkers among HC and YLWH. Correlations distinct to YLWH were predominantly between biomarkers of macrophage and vascular inflammation. PCA of outcome groups showed HC and suppressed YLWH clustering together for lymphocyte activation biomarkers, whereas macrophage activation markers showed all YLWH clustering distinct from HC. Cardiovascular biomarkers were indistinguishable across groups. Averaged variable importance projection to assess single biomarkers that maximally contribute to discriminate among outcome groups identified soluble CD27, CD14, and CD163 as the 3 most important with TNFα and LPS also highly relevant in providing separation.</p><p><b>CONCLUSIONS: </b>Soluble inflammatory and lymphocyte biomarkers sufficiently distinguish YLWH from HC. Persistent macrophage activation biomarkers may provide a means to monitor consequences of HIV infection in fully suppressed YLWH.</p>

DOI10.1002/JLB.3A0717-294RR
Alternate JournalJ. Leukoc. Biol.
PubMed ID29377283
PubMed Central IDPMC6528780
Grant ListU01 HD040533 / HD / NICHD NIH HHS / United States
U01 HD040474 / HD / NICHD NIH HHS / United States
UL1 RR025780 / RR / NCRR NIH HHS / United States
U01 AI068632 / AI / NIAID NIH HHS / United States
UL1 RR024131 / RR / NCRR NIH HHS / United States
R01 DA031017 / DA / NIDA NIH HHS / United States
U01 DA044571 / DA / NIDA NIH HHS / United States
M01 RR010284 / RR / NCRR NIH HHS / United States
P30 AI064518 / AI / NIAID NIH HHS / United States
UL1 RR024134 / RR / NCRR NIH HHS / United States
M01 RR020359 / RR / NCRR NIH HHS / United States