Quantitative assessment of IgM antibodies towards an immunodominant B-cell epitope within the preS2 domain of HBV in the natural course and during combined prednisone/interferon alpha 2b treatment of chronic hepatitis B virus infection.
A direct binding enzyme-linked immunosorbent assay (ELISA) was established for quantitative determination of serum IgM antibodies towards a synthetic peptide corresponding to a selected segment (14-21) of the preS2-gene product containing an immunodominant linear B-cell epitope. The prevalence of IgM anti-preS2 (14-21) antibody titers > 1,000 for hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B virus (HBV) infection was 38% (22/58) and 10% (2/21) for HBeAg-negative subjects (P < 0.005). IgM anti-preS2 (14-21) reactivity was detected during the clinical course of chronic HBV infection and IgM anti-peptide antibody titers declined and disappeared before spontaneous HBe/anti-HBe seroconversion. Recombinant interferon (IFN)-alpha 2b with an antecedent short course of corticosteroids was administered to eight Chinese 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 presence of pretreatment IgM anti-preS2 (14-21) in serum and the capacity to respond favorably to the combined prednisone/IFN-alpha 2b therapy was detected. The IgM anti-preS2 (14-21) titers decreased during treatment with subsequent loss of detectable antibodies 8-16 weeks after the initiation of therapy. This decrease was concomitant with an alanine aminotransferase (ALT) augmentation preceding the disappearance of HBV-DNA and anti-HBe seroconversion. Long-term remission was not observed in treated patients who lacked detectable levels of pretreatment IgM anti-preS2 (14-21) in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Fei
G Z
GZ
Department of Environmental Health and Infectious Disease Control, Karolinska Hospital, Stockholm, Sweden.
Sylvan
S P
SP
Hellström
U B
UB
Yao
G B
GB
D000293:Adolescent; D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D006509:Hepatitis B / Q000097:blood / Q000276:immunology* / Q000628:therapy; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006513:Hepatitis B e Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007370:Interferon Type I / Q000627:therapeutic use; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011241:Prednisone / Q000627:therapeutic use; D011498:Protein Precursors / Q000276:immunology*; D011994:Recombinant Proteins
D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011498:Protein Precursors; D011994:Recombinant Proteins; C050807:presurface protein 2, hepatitis B surface antigen; D011241:Prednisone