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

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.