title: During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy.
abstract: BACKGROUND
  Immune activation predicts morbidity during hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, although mechanisms underlying immune activation are unclear. Plasma levels of autotaxin and its enzymatic product, lysophosphatidic acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown.
  
  
  METHODS
  We evaluated plasma levels of autotaxin, interleukin 6 (IL-6), soluble CD14 (sCD14), soluble CD163 (sCD163), and Mac2 binding protein (Mac2BP) during HCV infection, HIV infection, and HCV-HIV coinfection, as well as in uninfected controls, before and after HIV antiretroviral therapy (ART) initiation and during interferon-free HCV therapy.
  
  
  RESULTS
  We observed greater plasma autotaxin levels in HCV-infected and HCV-HIV-coinfected participants, compared with uninfected participants, primarily those with a higher ratio of aspartate aminotransferase level to platelet count. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA levels in HCV-infected participants and with Mac2BP levels in HCV-HIV-coinfected participants, while in HIV-infected individuals, sCD14 levels correlated with Mac2BP levels. Autotaxin, LPA, and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting interferon-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting ART for HIV infection. In vitro, LPA activated monocytes.
  
  
  CONCLUSIONS
  These data indicate that elevated levels of autotaxin and soluble markers of immune activation during HCV infection are partially reversible within 6 months of initiating interferon-free HCV treatment and that autotaxin may be causally linked to immune activation during HCV infection and HCV-HIV coinfection.
authors.affiliation: Department of Medicine.
authors.forename: Lenche
authors.initials: L
authors.lastname: Kostadinova
authors.affiliation: Department of Medicine.
authors.forename: Carey L
authors.initials: CL
authors.lastname: Shive
authors.affiliation: Department of Pathology.
authors.forename: Chelsey
authors.initials: C
authors.lastname: Judge
authors.affiliation: Department of Medicine.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zebrowski
authors.affiliation: Department of Medicine.
authors.forename: Anita
authors.initials: A
authors.lastname: Compan
authors.affiliation: Department of Medicine.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Rife
authors.affiliation: Department of Medicine.
authors.forename: Amy
authors.initials: A
authors.lastname: Hirsch
authors.affiliation: Department of Medicine.
authors.forename: Yngve
authors.initials: Y
authors.lastname: Falck-Ytter
authors.affiliation: Department of Proteomics.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Schlatzer
authors.affiliation: Department of Proteomics.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Proteomics.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Chance
authors.affiliation: Department of Medicine.
authors.forename: Benigno
authors.initials: B
authors.lastname: Rodriguez
authors.affiliation: Department of Dermatology, Cleveland VA Medical Center, University Hospitals Case Medical Center, Case Center for AIDS Research, Case Western Reserve University, Ohio.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Popkin
authors.affiliation: Department of Medicine.|Department of Pathology.
authors.forename: Donald D
authors.initials: DD
authors.lastname: Anthony
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D060085:Coinfection / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D005260:Female; D006678:HIV / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D015850:Interleukin-6 / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008246:Lysophospholipids / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000821:virology; D010727:Phosphoric Diester Hydrolases / Q000097:blood*; D010949:Plasma / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology; D000098902:CD163 Antigen; D000099189:Lysophospholipase D
chemical_list: D019380:Anti-HIV Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D007372:Interferons; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid
keywords: T cell; ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2); hepatitis C; human; immunity; lysophospholipase D; monocyte