Lack of suppressive antibody activity in sera from patients with active-phase autoimmune diseases

To investigate the presence of a suppressive antibody activity in sera from patients with autoimmune diseases, the IgG autoreactivity in whole serum was compared to that of the IgG fraction purified by affinity chromatography on protein G-sepharose. Competitive inhibition assays on the binding to histone, dsDNA, RNP and thyroglobulin of the purified IgG fraction by the autologous IgM present in serum without IgG and depleted of <100 kD components (named IgM fraction) were also performed. The IgG reactivity to the autoantigens tested was considerably increased in the IgG fraction than in the whole serum drawn from a healthy control and from three SLE patients in an inactive-phase of disease. Addition of the IgM fraction to the autologous purified IgG resulted in a dose-dependent inhibition of IgG binding to the autoantigens tested. However, no differences were observed between the autoreactivity of the IgG in whole serum and that of the purified IgG fraction from active-phase SLE patients, or from two patients with autoimmune thyroiditis, and the autologous IgM fractions did not inhibit significantly binding to the autoantigens under study of the purified IgG fraction. Our findings support the concept that the IgG autoreactivity in physiological conditions is regulated by idiotypic interactions between IgG and IgM, and suggest that this regulation is broken in the active phase of autoimmune diseases and that clinical remission from SLE could be associated with the restoration of this control mechanism. Additionally, qualitative differences, such as polyreactivity or change of idiotype in the autoreactive IgG fraction from active-phase disease might contribute to escape of regulation.