Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection.

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.

• Authors: 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, Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study) Investigators
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 210 Issue 9 Pg. 1396-406 (Nov 01 2014) ISSN: 1537-6613 [Electronic] United States
• PMID: 24813472 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• Biomarkers
• CD163 antigen
• Fibrin Fibrinogen Degradation Products
• Interleukin-6
• Lipopolysaccharide Receptors
• Receptors, Cell Surface
• fibrin fragment D
• C-Reactive Protein

Topics

• Adult
• Antigens, CD (blood)
• Antigens, Differentiation, Myelomonocytic (blood)
• Biomarkers (blood)
• Blood Coagulation (physiology)
• C-Reactive Protein (analysis)
• Female
• Fibrin Fibrinogen Degradation Products (analysis)
• HIV Infections (blood, immunology, physiopathology)
• Humans
• Inflammation (blood, physiopathology)
• Interleukin-6 (blood)
• Lipopolysaccharide Receptors (blood)
• Male
• Middle Aged
• Monocytes (physiology)
• Phenotype
• Receptors, Cell Surface (blood)
• T-Lymphocytes (physiology)