title: 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.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Eleanor M P
authors.initials: EM
authors.lastname: Wilson
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Amrit
authors.initials: A
authors.lastname: Singh
authors.affiliation: Division of Biostatistics.
authors.forename: Katherine Huppler
authors.initials: KH
authors.lastname: Hullsiek
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dave
authors.initials: D
authors.lastname: Gibson
authors.affiliation: Department of Medicine, University of Minnesota Washington University School of Medicine, St. Louis, Missouri.
authors.forename: W Keith
authors.initials: WK
authors.lastname: Henry
authors.affiliation: National Jewish Health, Denver, Colorado.
authors.forename: Ken
authors.initials: K
authors.lastname: Lichtenstein
authors.affiliation: Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Nur F
authors.initials: NF
authors.lastname: Önen
authors.affiliation: Miriam Hospital, Providence, Rhode Island.
authors.forename: Erna
authors.initials: E
authors.lastname: Kojic
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Pragna
authors.initials: P
authors.lastname: Patel
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: John T
authors.initials: JT
authors.lastname: Brooks
authors.affiliation: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Irini
authors.initials: I
authors.lastname: Sereti
authors.affiliation: Department of Medicine, University of Minnesota Division of Infectious Diseases, Hennepin County Medical Center, Minneapolis, Minnesota.
authors.forename: Jason V
authors.initials: JV
authors.lastname: Baker
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000097:blood; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation / Q000502:physiology; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000097:blood; D013601:T-Lymphocytes / Q000502:physiology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D011956:Receptors, Cell Surface; C036309:fibrin fragment D; D002097:C-Reactive Protein
keywords: C-reactive protein; D-dimer; HIV; IL-6; immune activation; monocytes