HBcAg expressed on the surface of circulating dane particles in patients with hepatitis B virus infection without evidence of anti‐HBc formation

Abstract

Circulating immune complexes composed of HBcAg and anti‐HBc have been demonstrated recently in patients with hepatitis B virus replication. After dissociation of immune complexes by chaotropic ions, HBcAg was quantified radioimmunologically. In the present study, we describe 10 patients with hepatitis B virus replication, absent or delayed anti‐HBc formation and exposed HBcAg in serum. Four of the 10 patients had acute hepatitis, and six patients had chronic persistent hepatitis. In seven of 10 patients, a secondary immune defect was apparent due to acquired immunodeficiency syndrome, leukemia, histiocytosis X, sarcoidosis or end‐stage renal disease. Electron microscopy demonstrated that Dane particles from anti‐HBc‐negative patients were agglutinated after addition of monoclonal anti‐HBc antibodies, whereas Dane particles from anti‐HBc‐positive sera did not show agglutination. Monoclonal HBsAg‐specific antibodies aggregated Dane particles independent of the presence of anti‐HBc. Circulating HBcAg was always associated with the Dane particle fraction after density gradient separation. Hepatitis B virus core proteins from patients with and without anti‐HBc studied by immunoblotting after sodium dodecyl sulfate‐gel electrophoresis showed identical patterns. Hepatocytes from anti‐HBc‐negative patients were positive for HBcAg but negative for immunoglobulin G by immunofluorescence technique. The data indicate that HBcAg may also be expressed on the surface of Dane particles, where it is commonly masked by anti‐HBc. Copyright © 1989 American Association for the Study of Liver Diseases