Anti‐idiotypes against Autoantibodies in Normal Immunoglobulins: Evidence for Network Regulation of Human Autoimmune Responses

This manuscript summarizes observations indicating that anti-idiotypes against human autoantibodies may be found in sera from patients recovered from autoimmune disease and in pooled normal polyspecific immunoglobulins (IVIg). The evidence that IVIg contain anti-idiotypes against autoantibodies includes: 1) inhibition by F(ab)2 from IVIg of the binding of F(ab)2 autoantibodies to their autoantigens; 2) specific retention of autoantibodies upon affinity chromatography of F(ab)2 fragments containing autoantibody activity on Sepharose-bound F(ab)2 from IVIg; 3) lack of detection of anti-allotypes and lack of significant anti-Fc activity in IVIg; 4) specific competitive displacement by polyclonal heterologous F(ab)2 anti-idiotypes of the binding of IVIg to affinity-purified F(ab)2 autoantibodies. The high number of donors contributing to IVIg endows the preparations with anti-idiotypic specificities that may not necessarily be detectable in plasma from single healthy individuals. Our observations of the presence in IVIg of anti-idiotypes against pathogenic autoantibodies and against IgG and IgM autoantibodies found in low amounts in normal sera supports the concept of a functional network regulating expression of autoimmunity in humans. We suggest that IVIg may be efficient in selected autoimmune diseases by providing a source of anti-idiotypes with a wide range of specificities brought as interconnected antibody species that may conpensate for altered connectivity of the immune network of patients with autoimmune diseases.