title: Peripheral blood monocyte subsets predict antiviral response in chronic hepatitis C.
abstract: BACKGROUND
  Hepatitis C virus infection evolves into chronic progressive liver disease in a significant percentage of patients. Monocytes constitute a diverse group of myeloid cells that mediate innate and adaptive immune response. In addition to proinflammatory CD16+ monocytes, a Tie-2+ subgroup - Tie-2 expressing monocytes (TEMs) - that has robust proangiogenic potential has been recently defined.
  
  
  OBJECTIVE
  To study the heterogeneity of peripheral blood monocytes in chronic hepatitis C (CHC) patients and to examine their proposed pathophysiological roles on disease progression and response to antiviral therapy.
  
  
  METHODS
  We studied CD16+ and Tie-2+ peripheral monocyte subpopulations in 21 healthy subjects and 39 CHC patients in various stages of disease and responses to antiviral treatment using flow cytometry. Expression profiles of proangiogenic and tissue remodelling factors in monocyte supernatants were measured using ELISA and protein arrays. Intrahepatic expression of CD14, CD31 and Tie-2 was analysed using immunofluorescence.
  
  
  RESULTS
  Increases of certain peripheral monocyte subsets were observed in the blood of CHC patients, wherein those cells with proinflammatory (CD16+) or proangiogenic (TEMs) potential expanded (P < 0.005, both). Notably, TEMs were significantly increased in nonresponders, particularly those with lower CD16 expression. In addition, many angiogenic factors were differentially expressed by peripheral monocytes from control or CHC patients, such as angiopoietin-1 and angiogenin (P < 0.05). Interestingly, intrahepatic TEMs were distinguished within portal infiltrates of CHC patients.
  
  
  CONCLUSIONS
  These findings suggest for the first time the relevance of peripheral monocytes phenotypes for the achievement of response to treatment. Hence, the study of monocyte subset regulation might effect improved CHC prognoses and adjuvant therapies.
authors.affiliation: Liver Unit, IIS Hospital Universitario de la Princesa, Universidad Autónoma de Madrid & Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
authors.forename: Y
authors.initials: Y
authors.lastname: Rodríguez-Muñoz
authors.forename: S
authors.initials: S
authors.lastname: Martín-Vílchez
authors.forename: R
authors.initials: R
authors.lastname: López-Rodríguez
authors.forename: A
authors.initials: A
authors.lastname: Hernández-Bartolomé
authors.forename: M
authors.initials: M
authors.lastname: Trapero-Marugán
authors.forename: M J
authors.initials: MJ
authors.lastname: Borque
authors.forename: R
authors.initials: R
authors.lastname: Moreno-Otero
authors.forename: P
authors.initials: P
authors.lastname: Sanz-Cameno
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D058851:GPI-Linked Proteins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy; D006801:Humans; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D011237:Predictive Value of Tests; D042787:Receptor, TIE-2 / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D042787:Receptor, TIE-2