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PreS antigen expression and anti-preS response in hepatitis B virus infections: relationship to serum HBV-DNA, intrahepatic HBcAg, liver damage and specific T-cell response

  • Marie-Anne Petit
  • F. Capel
  • F. Zoulim
  • S. Dubanchet
  • I. Chemin
  • A. Penna
  • C. Ferrari
  • C. Trépo
Conference paper
Part of the Archives of Virology book series (ARCHIVES SUPPL, volume 4)

Summary

The diagnostic value of preS antigens and anti-preS antibodies during Hepatitis B virus (HBV) infections have not yet been clearly elucidated. Therefore, the objectives of this study were: 1) to better under¬stand the clinical significance of the expression of both preSl and preS2 antigens (preSlAg and preS2Ag) in the serum of chronic HBsAg carriers, and 2) to define the respective role of antibody responses to HBs-, preS2-and preSl -specific determinants in the course of acute hepatitis B (AH-B) infections with different outcomes.

Our data showed that the serum preSlAg/HBsAg ratio correlated well with the level of viral replication (serum HBV-DNA as monitored by PCR assay and liver HBcAg), especially in anti-HBe positive chronic carriers. The complete eradication of virions required a persistent antibody response to conformation-dependent HBs-epitopes, temporally associated with a vigorous T cell response to nucleocapsid antigens. Recovery from hepatitis B can be achieved when there is no early antibody response to preS2- and preSl-proteins, which was found to be transient, concomitant with a flare-up of the liver disease, and preceding anti-HBs production.

Information on the patterns of preS antigens and their antibodies remained clouded because of the varying specificities and sensitivities of research methods used in studies to date. We have, therefore, developed original Polyclonal-Monoclonal RadioImmunoAssays (PAb-MAb RIAs) [5, 8] by using monoclonal antibodies (MAbs) having previously well-defined specificities [3, 4, 5, 7]. We could thus detect and quantify simultaneously the three distinct antigenicities of the HBV envelope, HBsAg, preS2Ag and preSlAg, with the same sensitivity. In this way, the preSlAg/HBsAg and preS2Ag/HBsAg ratios can be calculated to estimate the serum expression of both preSlAg and preS2Ag in relation to total HBsAg activity during different stages of chronic HBV infection. For optimal management of the state of HBV replication in chronic viral infection, the detection of HBV-DNA in serum was monitored by the Polymerase Chain Reaction (PCR) assay [1].

We extended our work by investigating the clinical significance of antibody response to preS-specific determinants in patients with AH-B showing different outcomes in both natural course or response to α-interferon therapy. In a first attempt, we chose to use the Western Immuno-Blotting Assay (WIBA) to obtain a qualitative assessment of the nature of preS antibody responses [6]. Finally, the cell-mediated immune response to HBV antigens was also studied in several patients with self-limited AH-B [2] leading to a relevant finding which may help to clarify the mechanisms responsible for complete clearance of HBV.

Keywords

Hepatitis Delta Virus Chronic HBsAg Carrier PreS Antigen Nucleocapsid Antigen Intrahepatic HBcAg 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Chemin I, Baginski I, Petit M-A, Zoulim F, Pichoud C, Capel F, Hantz O, Trepo C (1991) Correlation between HBV DNA detection by PCR and preSl antigenemia in symptomatic and asymptomatic HBV infections. J Med Virol 33: 51–57PubMedCrossRefGoogle Scholar
  2. 2.
    Ferrari C, Penna A, Bertoletti A, Valli A, Antoni AD, Giuberti T, Cavalli A, Petit M-A, Fiaccadori F (1990) Cellular immune response to hepatitis B virus-encoded antigens in acute and chronic hepatitis B virus infection. J Immunol 145: 3442–3449PubMedGoogle Scholar
  3. 3.
    Neurath AR, Strick N, Kent SBH, Parker K, Courouce A-M, Riottot M-M, Petit M-A, Budkowska A, Girard M, Piilot J (1987) Antibodies to synthetic peptides from the preSl and preS2 regions of one subtype of the hepatitis B virus (HBV) envelope protein recognize all HBV subtypes. Mol Immunol 24: 975–980PubMedCrossRefGoogle Scholar
  4. 4.
    Petit M-A, Capel F, Riottot M-M, Dauguet C, Piilot J (1987) Antigenic mapping of the surface proteins of infectious hepatitis B virus particles. J Gen Virol 68: 2759–2767PubMedCrossRefGoogle Scholar
  5. 5.
    Petit M-A, Dubanchet S, Capel F (1989) A monoclonal antibody specific for the hepatocyte receptor binding site on hepatitis B virus. Mol Immunol 26: 531—537PubMedCrossRefGoogle Scholar
  6. 6.
    Petit M-A, Maillard P, Capel F, Piilot J (1986) Immunochemical structure of the hepatitis B surface antigen vaccine-II. Analysis of antibody responses in human sera against the envelope proteins. Mol Immunol 23: 511–523PubMedCrossRefGoogle Scholar
  7. 7.
    Petit M-A, Strick N, Dubanchet S, Capel F, Neurath AR (1991) Inhibitory activity of monoclonal antibody F35.25 on the interaction between hepatocytes (HepG2 cells) and preSl-specific ligands. Mol Immunol 28: 517–521PubMedCrossRefGoogle Scholar
  8. 8.
    Petit M-A, Zoulim F, Capel F, Dubanchet S, Dauguet C, Trepo C (1990) Variable expression of preSl antigen in serum during chronic hepatitis B virus infection: an accurate marker for the level of hepatitis B virus replication. Hepatology 11: 809–814PubMedCrossRefGoogle Scholar
  9. 9.
    Trepo C, Chemin I, Petit M-A, Chossegros P, Zoulim F, Chevallier P, Sepetjan M (1990) Possible prevention of chronic hepatitis B by early interferon therapy. J Hepatol 11: S95–S99PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • Marie-Anne Petit
    • 1
  • F. Capel
    • 1
  • F. Zoulim
    • 2
  • S. Dubanchet
    • 1
  • I. Chemin
    • 2
  • A. Penna
    • 3
  • C. Ferrari
    • 3
  • C. Trépo
    • 2
  1. 1.INSERM Unité 131 Immunopathology & Viral ImmunologyClamartFrance
  2. 2.INSERM Unité 271LyonFrance
  3. 3.Cattedra Malattie InfettiveUniversité di ParmaParmaItaly

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