title: Activating NK cell receptor expression/function (NKp30, NKp46, DNAM-1) during chronic viraemic HCV infection is associated with the outcome of combined treatment.
abstract: Specific NK cell killer inhibitory receptor (KIR):HLA haplotype combinations have been associated with successful clearance of acute and chronic HCV infection. Whether an imbalance of activating NK cell receptors also contributes to the outcome of treatment of chronic HCV infection, however, is not known. We studied peripheral NK cell phenotype and function in 28 chronically viraemic HCV genotype I treatment-naïve patients who underwent treatment with pegylated IFN-α and ribavirin. At baseline, chronically infected patients with sustained virological response (SVR) had reduced CD56(bright) CD16(+/-)  cell populations, increased CD56(dull) CD16(+)  NK cell proportions, and lower expression of NKp30, DNAM-1, and CD85j. Similarly, reduced NK cell IFN-γ production but increased degranulation was observed among nonresponding (NR) patients. After treatment, CD56(bright) CD16(+/-)  NK cell numbers increased in both SVR and NR patients, with a parallel significant increase in activating NKp30 molecule densities in SVR patients only. In vitro experiments using purified NK cells in the presence of rIL-2 and IFN-α confirmed upregulation of NKp30 and also of NKp46 and DNAM-1 in patients with subsequent SVR. Thus, differences in patient NK cell receptor expression and modulation during chronic HCV-1 infection are associated with subsequent outcome of standard treatment. Individual activating receptor expression/function integrates with KIR:HLA genotype carriage to determine the clearance of HCV infection upon treatment.
authors.affiliation: Istituto G.Gaslini, Genova, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Bozzano
authors.forename: Antonino
authors.initials: A
authors.lastname: Picciotto
authors.forename: Paola
authors.initials: P
authors.lastname: Costa
authors.forename: Francesco
authors.initials: F
authors.lastname: Marras
authors.forename: Valentina
authors.initials: V
authors.lastname: Fazio
authors.forename: Ivan
authors.initials: I
authors.lastname: Hirsch
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Andrea
authors.initials: A
authors.lastname: De Maria
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D000998:Antiviral Agents / Q000627:therapeutic use; D019002:CD56 Antigen / Q000096:biosynthesis; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008297:Male; D008875:Middle Aged; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism*; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D017452:Receptors, IgG / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D016896:Treatment Outcome; D014766:Viremia / Q000276:immunology; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000998:Antiviral Agents; D000098862:T Lineage-Specific Activation Antigen 1; D019002:CD56 Antigen; D016898:Interferon-alpha; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; C112260:NCR1 protein, human; C431710:NCR3 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D055628:Natural Cytotoxicity Triggering Receptor 3; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a