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Eleanor M. P. Wilson, Amrit Singh, Katherine Huppler Hullsiek, Dave Gibson, W. Keith Henry, Ken Lichtenstein, Nur F. Önen, Erna Kojic, Pragna Patel, John T. Brooks, Irini Sereti, Jason V. Baker, for the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) Investigators, Monocyte-Activation Phenotypes Are Associated With Biomarkers of Inflammation and Coagulation in Chronic HIV Infection, The Journal of Infectious Diseases, Volume 210, Issue 9, 1 November 2014, Pages 1396–1406, https://doi.org/10.1093/infdis/jiu275
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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.
- phenotype
- hiv
- acquired immunodeficiency syndrome
- inflammatory markers
- inflammation
- cd14 antigen
- biological markers
- blood coagulation
- cryopreservation
- immunophenotyping
- monocytes
- plasma
- chemokine (c-c motif) receptor 5
- t-lymphocytes
- c-reactive protein
- interleukin-6
- mortality
- fibrin fragment d substance
- hiv, chronic infection with
- blood hiv rna
- t-cell activation
- coagulation process
- antigens, cd16
