Anti-idiotypic antibodies and autoantibodies

Abstract

In this paper, we have provided experimental evidence that antibodies to autoantigens bear common idiotypes and that this property makes them susceptible to anti-idiotypic regulation. Spontaneously occurring autoantibodies to Tg in rats have been extensively investigated as a model of immune response responsible for the appearance of autoimmune disease. Large idiotypic cross-reactivity was found among autoantibodies of various individual animals. Similarly, a high degree of idiotypic relatedness was found among mouse monoclonal antibodies reacting with a highly conserved antigenic domain of thyroglobulin. Both rat and mice idiotype were found to be present on spontaneous and induced antibodies to rat thyroglobulin from individuals of other species. In vivo experiments showed that anti-idiotypic antibodies can be effective in suppressing autoantibodies formation. In the induced TIN in BN rats, a single injection of anti-idiotypic serum prior to the induction of autoimmune disease was sufficient to generate a significant selective suppression of autoantibodies produced against a pathogenetic chemical form of the autoantigen, that is, the one against which the autoantibodies used to prepare the anti-idiotypic reagent as mostly reactive. Similarly, it was found that repeated injections of anti-idiotype into rats with ongoing spontaneous production of autoantibodies to thyroglobulin were able to significantly decrease the amount of circulating autoantibodies from the pretreatment values. Thus, although the beneficial effect of anti-idiotype observed in these experiments was only partial, indications were obtained that a specific anti-idiotypic immunity can be used to regulate autoantibody production. Finally, evidence has been provided to support the hypothesis that auto-anti-idiotype, as a normal constituent of the immune response, can be responsible for the potentiation of immune complex-mediated tissue injury that is often the hallmark of autoimmune diseases.