Antibody-directed complement-mediated cytotoxicity to hepatocytes from patients with chronic hepatitis B

Abstract

SUMMARYThe 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% (meanis.e.m,); n = 6) over that against hepatocytes from individuals with chronic persistent hepatitis or inactive liver cirrhosis (40-6±18-6%; « = 4) (P = 0019), Overall, values ofthe 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.

Development of anti-hepatitis B surface (HBs) antibodies after HBs antigen loss in HIV-hepatitis B virus co-infected patients

“…It would then be assumed that humoral responses linked to antibody production would play a dominant role in preventing HBV reactivation. Finally, HBsAg is expressed on the membrane of infected hepatocytes [26], to which recognition by anti-HBs antibodies could lead to cytotoxicity and clearance of infected liver cells [27]. There is, therefore, an inherent interest in studying how anti-HBs antibody production is achieved after HBsAg-loss.…”

Direct role of antibody‐secreting B cells in the severity of chronic hepatitis B

“…The number of hepatocytes in each well was counted. The quotient resulting from the division of the difference between mean number of cells in control and test wells was divided by mean number of cells in control (complement control) and this gave the percentage cytotoxicity [Michalak et al, ]. The experiment was repeated three times independently, each time in triplicate.…”

“…In chronic viral hepatitis, an enrichment of CD8 + cytotoxic/suppressor T cell was observed in liver and peripheral blood [Löhr et al, ]. Many investigators suggested the chronicity of HBV infection was caused by a deficient cellular immune function [Michalak et al, ; Khettry et al, ; Tülek et al, ]. Thus, T‐cell dysfunction might contribute towards viral persistence [You et al, ].…”

CD55 limits sensitivity to complement-dependent cytolysis triggered by heterologous expression of α-gal xenoantigen in colon tumor cells

“…Cytolysis assays were performed using trypan blue exclusion assays, which have been used in many previous studies and are still widely used today (2,20,26,42,45,58,65). Briefly, cells in the logarithmic growth phase were released from the culture flask using 3 mM EDTA and were washed.…”