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

Authors

  • Dr. Bernd Möller,

    Corresponding author
    1. Departments of Internal Medicine and Pediatric Medicine, Klinikum Rudolf Virchow, Standort Charlottenburg, Freie Universität Berlin, and Robert Koch-Institut des BGA, Berlin, Federal Republic of Germany
    • Medizinische Klinik, Universitätsklinikum Rudolf Virchow, Spandauer Damm 130, D-1000 Berlin 19, Federal Republic of Germany
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  • Uwe Hopf,

    1. Departments of Internal Medicine and Pediatric Medicine, Klinikum Rudolf Virchow, Standort Charlottenburg, Freie Universität Berlin, and Robert Koch-Institut des BGA, Berlin, Federal Republic of Germany
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  • Roman Stemerowicz,

    1. Departments of Internal Medicine and Pediatric Medicine, Klinikum Rudolf Virchow, Standort Charlottenburg, Freie Universität Berlin, and Robert Koch-Institut des BGA, Berlin, Federal Republic of Germany
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  • Günther Henze,

    1. Departments of Internal Medicine and Pediatric Medicine, Klinikum Rudolf Virchow, Standort Charlottenburg, Freie Universität Berlin, and Robert Koch-Institut des BGA, Berlin, Federal Republic of Germany
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  • Hans Gelderblom

    1. Departments of Internal Medicine and Pediatric Medicine, Klinikum Rudolf Virchow, Standort Charlottenburg, Freie Universität Berlin, and Robert Koch-Institut des BGA, Berlin, Federal Republic of Germany
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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.

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