Autoantibodies to isolated human hepatocyte plasma membranes in liver disease. I. Specificity for chronic active...

Circulating autoantibodies reacting with human hepatocyte plasma membranes (HHPM) were quantitated in acute and chronic liver disease using an enzyme-linked immunosorbent assay (ELISA). Anti-HHPM were found most frequently in patients with chronic active hepatitis (CAH), a disease postulated to result from autoimmune processes directed at organ-specific antigens on the surface of hepatocytes. The high incidence of anti-HHPM in CAH (75%) contrasted significantly with all other groups assayed, including primary biliary cirrhosis (44%), alcoholic liver disease (21%), acute viral hepatitis (17%), and chronic persistent hepatitis (8%). The titers of anti-HHPM in CAH were significantly greater than in other liver disease and control groups. Anti-HHPM quantitated by ELISA correlated with hepatocellular membrane staining by indirect immunofluorescence. Autoantibodies to HHPM were found with an equivalent frequency in three etiological subgroups of CAH: autoimmune CAH, hepatitis B virus (HBV)-related CAH, and CAH associated with excess alcohol consumption. Anti-HHPM of the IgG and IgA isotypes were found in the highest frequency. There was a trend for patients with a histologically more severe disease to have higher titers of anti-HHPM. Immunoblots of SDS-PAGE-separated HHPM showed antibodies to react with a number of polypeptides, some of which appeared human specific. These data suggest that isolated HHPM are a source of relevant hepatocellular membrane antigens. Further studies of the different antigenic specificities of anti-HHPM are required to define which of these may be of pathogenetic importance in chronic active hepatitis.