Serum antibodies against the hepatitis C virus E2 protein mediate antibody-dependent cellular cytotoxicity (ADCC).
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.
Nattermann
Jacob
J
Department of General Internal Medicine I, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany. jacob.nattermann@ukb.uni-bonn.de
Schneiders
Angelika Maria
AM
Leifeld
Ludger
L
Langhans
Bettina
B
Schulz
Monika
M
Inchauspé
Geneviève
G
Matz
Bertfried
B
Brackmann
Hans H
HH
Houghton
Michael
M
Sauerbruch
Tilman
T
Spengler
Ulrich
U
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
D018937:Hepatitis C Antibodies; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus