Antibody-directed complement-mediated cytotoxicity to hepatocytes from patients with chronic hepatitis B.
The susceptibility of hepatocytes from patients with chronic hepatitis B to complement-dependent cytotoxicity mediated by heterologous antibodies to hepatitis B virus core (anti-HBc) and surface (anti-HBs) antigens and to hepatic asialoglycoprotein receptor was examined using a microcytotoxicity assay. The anti-HBc-induced cytotoxicity was found to be markedly enhanced against hepatocytes isolated from patients with chronic active hepatitis (72.6 +/- 9.5% (mean +/- s.e.m.); n = 6) over that against hepatocytes from individuals with chronic persistent hepatitis or inactive liver cirrhosis (40.6 +/- 18.6%; n = 4) (P = 0.019). Overall, values of the anti-HBc-directed cytotoxicity were higher in patients positive for HBcAg in hepatocytes and seropositive for hepatitis B virus e antigen (HBeAg). Hepatocytotoxicity was also exerted by anti-HBs and anti-asialoglycoprotein receptor antibodies in the presence of complement, but it was not seemingly related to disease activity. These results indicate that hepatitis B virus core and surface antigens and asialoglycoprotein receptor at the hepatocyte surface can be recognized by antibodies, and raise the possibility that complement-dependent cytolysis may contribute to the injury of hepatitis B virus-infected hepatocytes. The data also suggest that liver cells of patients with severe chronic hepatitis might be more susceptible to anti-HBc antibody-directed complement-mediated cytotoxicity than those with inactive liver histology.
Michalak
T I
TI
Liver Research Laboratory, Faculty of Medicine, Memorial University of Newfoundland, St John's, Canada.
Lau
J Y
JY
McFarlane
B M
BM
Alexander
G J
GJ
Eddleston
A L
AL
Williams
R
R
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity; D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D002908:Chronic Disease; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D006509:Hepatitis B / Q000276:immunology*; D006512:Hepatitis B Core Antigens / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000276:immunology
D037263:Asialoglycoprotein Receptor; D001212:Asialoglycoproteins; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D011956:Receptors, Cell Surface; D003165:Complement System Proteins