An IgM-specific anti-[anti-HBs] antibody was detected by radioimmunoassay using anti-IgMcoated beads and '261-labeled anti-HBs. This antiidiotype was found only in the sera of hepatitis B virus-infected patients, both acute and chronic. However, not all HBsAg-positive patients exhibited this reaction, and activity was correlated with the presence of HBeAg. Approximately 93% of sera that contained antiidiotype activity also contained HBeAg. Conversely, 70% of the sera positive for HBeAg reacted in the IgM assay. No correlation was observed between the presence of antiidiotype and rheumatoid factor or elevated SGPT levels.
Two approaches were used to determine whether the reactive moiety was an IgM anti-[anti-HBs] as postulated or an IgM anti-HBs/HBsAg complex. It was shown that chicken anti-HBs sera, which does not share the common idiotype of human and other mammalian anti-HBs, did not block a positive reaction in this radioimmunoassay even though it specifically bound HBsAg. It was also demonstrated that treatment with polyethylene gylcol, which will precipitate IgM anti-HBs/HBsAg activity, did not precipitate the reactive moiety in 6 of 7 sera tested, lending further evidence to the existence of an IgM antiidiotype in these patients.
It is suggested that this antiidiotype directed against anti-HBs may be involved in a defective feedback mechanism resulting in the suppression of production of anti-HBs and maintenance of the carrier state.
Circulating immune complexes are frequently found in the blood of patients with acute or chronic hepatitis type B (1-5). Recently, Palla and coworkers (6-8) reported the apparent presence of HBsAg/IgM-specific anti-HBs complexes in acute and chronic hepatitis B and indicated that the presence of these immune complexes may function as prognostic indicators of chronic evolution. We present data to indicate that some of these positive radioimmunoassay reactions might be due to IgM antiidiotypic molecules directed against the combining site region of the anti-HBs antibody and not to the presence of HBsAg/IgM-specific anti-HBs complexes.
Increased levels of specific antiidiotypes have been detected in sera following hyperimmunization with specific antigens (9-17). However, to our knowledge, this is the first report of an antiidiotype detected during a natural viral infection in humans. The recognition of its