IMMUNOGLOBULIN-M REACTIVITY TOWARDS THE IMMUNOLOGICALLY ACTIVE REGION SP75 OF THE CORE PROTEIN OF HEPATITIS-C VIRUS (HCV) IN CHRONIC HCV INFECTION

Serum samples from a cohort of patients with chronic hepatitis C virus (HCV) infection were assayed for IgM anti-HCV/core reactivity with a ''site-specific'' ELISA, in which the solid phase was charged with the synthetic polypeptide analogue corresponding to the first 75 amino acids of the HCV core antigen (sp75). Thirteen of 24 (54%) patients exhibited IgM anti-sp75 reactivity. Both high-titered (1/16,000-1/32,000) and low-titered (1/1,000-1/4,000) IgM anti-sp75 reactive sera were found. IgM anti-sp75 antibodies persisted in the circulation over a long period in patients with fluctuating abnormal ALT levels. There was a striking association between detection of specific IgM anti-sp75 reactivity and the presence of HCV RNA in serum. Thus 11 of 15 (73%) sera containing HCV RNA also contained IgM anti-sp75 antibodies, while none of the HCV RNA-negative sera were IgM anti-sp75 reactive. Five of 11 patients without detectable levels of specific IgM anti-sp75 antibodies had their ALT levels returned to normal within 8 months to 3 years. Furthermore, a significant correlation was noted between the specific IgM anti-sp75 titers and the concentration of total plasma IgM, indicating that the immunological active region sp75 within the capsid of HCV has the capacity to induce an IgM secretion, which constitutes a substantial portion of the total plasma IgM, in patients with chronic HCV infection. This secretion was T-cell dependent as demonstrated by in vitro experiments in which peripheral B lymphocytes, from IgM anti-sp75-seropositive patients with chronic HCV infection could be induced to produce specific IgM anti-sp75 antibodies when stimulated with low concentrations of the synthetic polypeptide sp75 in the presence of autologous T lymphocytes.