Ti. Michalak et al., ANTIBODY-DIRECTED COMPLEMENT-MEDIATED CYTOTOXICITY TO HEPATOCYTES FROM PATIENTS WITH CHRONIC HEPATITIS-B, Clinical and experimental immunology, 100(2), 1995, pp. 227-232
The susceptibility of hepatocytes from patients with chronic hepatitis
B to complement-dependent cytotoxicity mediated by heterologous antib
odies to hepatitis B virus core (anti-HBc) and surface (anti-HBs) anti
gens and to hepatic asialoglycoprotein receptor was examined using a m
icrocytotoxicity 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, v
alues of the anti-HBc-directed cytotoxicity were higher in patients po
sitive for HBcAg in hepatocytes and seropositive for hepatitis B virus
e antigen (HBeAg). Hepatocytotoxicity was also exerted by anti-HBs an
d anti-asialoglycoprotein receptor antibodies in the presence of compl
ement, but it was not seemingly related to disease activity. These res
ults indicate that hepatitis B virus core and surface antigens and asi
aloglycoprotein receptor at the hepatocyte surface can be recognized b
y antibodies, and raise the possibility that complement-dependent cyto
lysis may contribute to the injury of hepatitis B virus-infected hepat
ocytes. The data also suggest that liver cells of patients with severe
chronic hepatitis might be more susceptible to anti-HBc antibody-dire
cted complement-mediated cytotoxicity than those with inactive liver h
istology.