title: Natural killer cell dynamic profile is associated with treatment outcome in patients with chronic HCV infection.
abstract: OBJECTIVE
  A substantial proportion of patients with chronic hepatitis C virus infection treated with pegylated interferon α/ribavirin fail to achieve sustained virological response (SVR). Since growing evidence suggests that innate immunity may influence treatment responses, we examined natural killer (NK) cell phenotypic and functional changes during standard antiviral therapy.
  
  
  METHODS
  Expression of several NK-cell regulatory molecules was evaluated by flow cytometry in 37 consecutive patients with chronic HCV infection at baseline and at different time points during and after discontinuation of treatment. Cytokine production was evaluated by intracellular staining. Cytolytic potential was assessed as degranulation and as antibody-dependent cytotoxicity.
  
  
  RESULTS
  Baseline frequencies of CD56(dim) NK cells and perforin content were significantly higher, whereas CD16 expression was lower in SVR vs. non-responder subjects. Analysis by linear regression for repeated measures during the first 12 weeks showed significantly increased frequencies of activated (CD69(+)) NK cells in rapid virological responders (RVR) and identified a typical NK cell profile associated with SVR, featuring higher NK perforin content, lower CD16 expression, and higher proportion of CD56(dim)/CD16(-) cells. Moreover, SVR patients displayed higher natural and antibody-dependent NK cell cytotoxicity. IL28B rs12979860 CC homozygosis was significantly associated with SVR, independently of NK-cell phenotype and function.
  
  
  CONCLUSIONS
  Different NK-cell phenotypic and functional features, in patients with chronic hepatitis C treated with standard therapy, were observed between non-responder vs. SVR patients, suggesting a potential role of NK cells in the response to treatment.
authors.affiliation: Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Oliviero
authors.forename: Dalila
authors.initials: D
authors.lastname: Mele
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Degasperi
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.forename: Eleonora
authors.initials: E
authors.lastname: Cremonesi
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Rumi
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Varchetta
authors.forename: Stefania
authors.initials: S
authors.lastname: Mantovani
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.forename: Mario U
authors.initials: MU
authors.lastname: Mondelli
mesh_terms: D000920:Antibody-Dependent Cell Cytotoxicity; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism; D054353:Perforin; D011092:Polyethylene Glycols / Q000627:therapeutic use; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D011446:Prospective Studies; D017452:Receptors, IgG / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D016898:Interferon-alpha; C522918:NCAM1 protein, human; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; C510468:PRF1 protein, human; D052899:Pore Forming Cytotoxic Proteins; D017452:Receptors, IgG; D011994:Recombinant Proteins; D054353:Perforin; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a