title: Lack of Siglec-7 expression identifies a dysfunctional natural killer cell subset associated with liver inflammation and fibrosis in chronic HCV infection.
abstract: Sialic-acid-binding immunoglobulin-like lectin-7 (Siglec-7) is a natural killer (NK) cell inhibitory receptor associated with NK phenotypic and functional abnormalities in HIV-1 infection. We investigated the significance of NK-expressed and serum soluble Siglec-7 in relation to NK functional ability and parameters of liver necroinflammation and fibrosis in chronic HCV infection.
  
  
  
  NK-expressed and serum Siglec-7 were evaluated in 130 and 166 HCV-infected individuals by flow cytometry and ELISA, respectively. NK cell degranulation and cytokine secretion were determined by flow cytometry. 65 patients with chronic HBV infection, 84 with chronic biliary disorders and 168 healthy donors served as controls.
  
  
  
  Expression of Siglec-7 was significantly decreased on NK cells from HCV-infected and HBV-infected patients and, conversely, serum Siglec-7 was significantly increased in these patients compared with controls. The frequency of Siglec-7pos NK cells was significantly higher at baseline in sustained virological responders to pegylated interferon-α/ribavirin treatment than in non-responders. Activating receptor expression was significantly higher in Siglec-7pos NK cells and was associated with increased degranulation and cytokine secretion compared with Siglec-7negcells. In chronic HCV infection, there was an inverse correlation between Siglec-7 expression and serum aminotransferases, γ-glutamyl transpeptidase, liver stiffness, aspartate aminotransferase to platelet ratio index and fibrosis-4 scores, and a positive correlation between serum Siglec-7 and the same clinical parameters, including histological staging.
  
  
  
  These findings identify Siglec-7negNK cells as a dysfunctional subpopulation associated with severe liver disease in chronic HCV infection.
authors.affiliation: Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Varchetta
authors.affiliation: Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Dalila
authors.initials: D
authors.lastname: Mele
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lombardi
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.affiliation: Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mantovani
authors.affiliation: Statistics and Clinical Epidemiology Service, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tinelli
authors.affiliation: Department of Transfusion Medicine, Azienda Ospedaliera della Provincia di Lecco, A. Manzoni Hospital, Lecco, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Spreafico
authors.affiliation: Department of Transfusion Medicine, Azienda Ospedaliera della Provincia di Lecco, A. Manzoni Hospital, Lecco, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Prati
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Ludovisi
authors.affiliation: Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Ferraioli
authors.affiliation: Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Filice
authors.affiliation: Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milano, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.affiliation: Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milano, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
authors.affiliation: Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and University of Milan, Milano, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Facchetti
authors.affiliation: Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bernuzzi
authors.affiliation: Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.affiliation: Research Laboratories, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.|Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
authors.forename: Mario U
authors.initials: MU
authors.lastname: Mondelli
mesh_terms: D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D016022:Case-Control Studies; D018450:Disease Progression; D005355:Fibrosis / Q000276:immunology / Q000473:pathology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000378:metabolism*; D037102:Lectins / Q000097:blood*; D010641:Phenotype; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D000637:Transaminases / Q000097:blood; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D037102:Lectins; C402206:SIGLEC7 protein, human; D005723:gamma-Glutamyltransferase; D000637:Transaminases; D001219:Aspartate Aminotransferases
keywords: CELLULAR IMMUNOLOGY; FIBROSIS; HEPATITIS B; HEPATITIS C; LIVER IMMUNOLOGY