title: Serum antibodies against the hepatitis C virus E2 protein mediate antibody-dependent cellular cytotoxicity (ADCC).
abstract: OBJECTIVE
  The role of antibody dependent cellular cytotoxicity (ADCC) in HCV infection is unclear at present. Antibodies mediating ADCC are usually directed against viral envelope proteins. As cell surface expression of the HCV envelope E2 protein has been shown, the HCV E2 protein is an especially promising candidate target for ADCC.
  
  
  METHODS
  Sera from patients with acute (n=6), self-limited (n=11) and chronic (n=19) HCV infection were analyzed in this study. Sera reacting with cell-bound HCV antigens were examined in a flowcytometric cytotoxicity assay using antigen-coated JOK-1 cells as targets.
  
  
  RESULTS
  We found that sera from all stages of HCV infection reacted with cells loaded with HCV E2. E2-specific ADCC was observed in patients with acute (n=3/6), self-limited (n=5/11) and chronic (n=13/19) hepatitis C and was closely related to fluorescence intensity in the E2-binding assay (r=0.67, P<0.001).
  
  
  CONCLUSIONS
  We conclude that E2-antibodies from all stages of HCV infection can mediate ADCC. Thus, the role of this process in the pathogenesis of chronic hepatitis C should be further elucidated.
authors.affiliation: Department of General Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. jacob.nattermann@ukb.uni-bonn.de
authors.forename: Jacob
authors.initials: J
authors.lastname: Nattermann
authors.forename: Angelika Maria
authors.initials: AM
authors.lastname: Schneiders
authors.forename: Ludger
authors.initials: L
authors.lastname: Leifeld
authors.forename: Bettina
authors.initials: B
authors.lastname: Langhans
authors.forename: Monika
authors.initials: M
authors.lastname: Schulz
authors.forename: Geneviève
authors.initials: G
authors.lastname: Inchauspé
authors.forename: Bertfried
authors.initials: B
authors.lastname: Matz
authors.forename: Hans H
authors.initials: HH
authors.lastname: Brackmann
authors.forename: Michael
authors.initials: M
authors.lastname: Houghton
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D016466:CHO Cells; D006224:Cricetinae; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D019562:Viral Load
chemical_list: D018937:Hepatitis C Antibodies; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus