title: NK cell phenotypic and functional shifts coincide with specific clinical phases in the natural history of chronic HBV infection.
abstract: Chronic HBV infection can be divided into 4 distinct clinical phases: immune tolerant, immune active, inactive carrier, and HBeAg-negative hepatitis. Using a systems biology approach, we recently identified innate immune response components, specifically NK cells as a distinctive factor of specific HBV clinical phases. To expand on this study and identify the underlying immunological mechanisms, we performed a comprehensive profiling of NK cells in chronic HBV infection.
  
  
  
  Peripheral blood from untreated chronic HBV patients was used to analyze phenotypic markers, as well as cytokine production and cytoxicity of NK cells.
  
  
  
  The overall composition, phenotype, and cytolytic activity of the NK cells remained constant across all clinical phases, with the exception of a few specific markers (KIRs, NKp46). CD56brightNK cells of chronic HBV patients differed in their ability to produce IFN-γ between the clinical phases pre- and post-HBeAg seroconversion.
  
  
  
  This depicts a shift in NK cell characteristics between the immune active, under heavy viral or immune pressure, and inactive carrier phases, that coincides with HBeAg seroconversion. Although these changes in NK cells do not appear to be completely responsible for differences in liver damage characteristic of specific clinical phases, they could provide a step toward understanding immune dysregulation in chronic HBV infection.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Rik A
authors.initials: RA
authors.lastname: de Groen
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Gertine W
authors.initials: GW
authors.lastname: van Oord
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Zwier M A
authors.initials: ZMA
authors.lastname: Groothuismink
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: van der Heide
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, The Netherlands. Electronic address: p.a.boonstra@erasmusmc.nl.
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D000328:Adult; D018959:CD57 Antigens / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics; D004279:DNA, Viral / Q000097:blood; D005260:Female; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014779:Virus Replication
chemical_list: D018959:CD57 Antigens; D016207:Cytokines; D004279:DNA, Viral; D007371:Interferon-gamma
keywords: Cytotoxicity; HBV clinical phases; Hepatitis B; IFN-γ; NK cells; Natural killer cells