TITLE

Monocyte-Activation Phenotypes Are Associated With Biomarkers of Inflammation and Coagulation in Chronic HIV Infection

AUTHOR(S)
Wilson, Eleanor M. P.; Singh, Amrit; Hullsiek, Katherine Huppler; Gibson, Dave; Henry, W. Keith; Lichtenstein, Ken; Önen, Nur F.; Kojic, Erna; Patel, Pragna; Brooks, John T.; Sereti, Irini; Baker, Jason V.
PUB. DATE
November 2014
SOURCE
Journal of Infectious Diseases;Nov2014, Vol. 210 Issue 9, p1396
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background. Soluble biomarkers of inflammation predict non-AIDS related morbidity and mortality among human immunodeficiency virus (HIV)–infected persons. Exploring associations between plasma biomarkers and cellular phenotypes may identify sources of excess inflammation.Methods. Plasma biomarkers (interleukin 6 [IL-6] level, D-dimer level, high-sensitivity C-reactive protein [hsCRP] level, soluble CD14 [sCD14] level, and soluble CD163 [sCD163] level) were measured from cryopreserved samples from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study). We performed immunophenotyping of peripheral blood mononuclear cells for markers of T-cell and monocyte activation, maturation, and migration. We evaluated associations between cellular phenotypes and soluble biomarkers by Spearman rank correlation and multivariate linear regression.Results. Participants' (n = 670) median age was 41 years, 88% were prescribed antiretroviral therapy, 72% had a plasma HIV RNA load of <400 copies/mL, and the median CD4+ T-lymphocyte count was 471 cells/µL. After adjustment, CD14++CD16+ monocytes were associated with higher levels of IL-6, hsCRP, and sCD163; associations with IL-6 and hsCRP persisted in persons with suppressed HIV replication. While CCR5+ monocytes positively associated with D-dimer levels, CCR2+ monocytes were inversely associated with hsCRP levels.Conclusions. Plasma inflammatory biomarkers that predict morbidity and mortality were strongly associated with monocyte activation and migration, modestly associated with T-cell maturation, and not associated with CD8+ T-cell activation phenotypes. These findings suggest that strategies to control monocyte activation warrant further investigation.
ACCESSION #
99224421

 

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