QUANTITATIVE ASSESSMENT OF IGM ANTIBODIES TOWARDS AN IMMUNODOMINANT B-CELL EPITOPE WITHIN THE PRES2 DOMAIN OF HBV IN THE NATURAL COURSE ANDDURING COMBINED PREDNISONE INTERFERON-ALPHA-2B TREATMENT OF CHRONIC HEPATITIS-B VIRUS-INFECTION

A direct binding enzyme-linked immunosorbent assay (ELISA) was establi shed for quantitative determination of serum IgM antibodies towards a synthetic peptide corresponding to a selected segment (14-21) of the p reS2-gene product containing an immunodominant linear B-cell epitope. The prevalence of IgM anti-preS2 (14-21) antibody titers >1,000 for he patitis B e antigen (HBeAg)-positive patients with chronic hepatitis B virus (HBV) infection was 38% (22/58) and 10% (2/21) for HBeAg-negati ve subjects (P < 0.005). IgM anti-preS2 (14-21) reactivity was detecte d during the clinical course of chronic HBV infection and IgM anti-pep tide antibody titers declined and disappeared before spontaneous HBe/a nti-HBe seroconversion. Recombinant interferon (IFN)-alpha 2b with an antecedent short course of corticosteroids was administered to eight C hinese patients with chronic HBV infection. The IgM anti-preS2 (14-21) reactivity was monitored consecutively during treatment and patients were followed for more than 1 year. A close association between the pr esence of pretreatment IgM anti-preS2 (14-21) in serum and the capacit y to respond favorably to the combined prednisone/IFN-alpha 2b therapy was detected. The IgM anti-preS2 (14-21) titers decreased during trea tment with subsequent loss of detectable antibodies 8-16 weeks after t he initiation of therapy. This decrease was concomitant with an alanin e aminotransferase (ALT) augmentation preceding the disappearance of H BV-DNA and anti-HBe seroconversion. Long-term remission was not observ ed in treated patients who lacked detectable levels of pretreatment Ig M anti-preS2 (14-21) in the circulation. These results demonstrate tha t a substantial cohort of HBeAg-positive chronic hepatitis B patients have IgM antibodies towards a synthetic B-cell epitope representing a dominant antibody binding site within the envelope of HBV. They indica te that IgM anti-preS2 (14-21) titers reflect the immunosuppressive ef fect on IgM secretion during the combined prednisone/IFN-alpha 2b ther apy. Further studies are needed to determine the usefulness of a quant itative assay for IgM anti-preS2 (14-21) measurements in predicting th e response to treatment with interferon alone or preceded by a short c ourse of prednisone in patients with chronic hepatitis B. (C) 1995 Wil ey-Liss, Inc.