The concept of anti-idiotypic regulation of selected autoimmune diseases by intravenous immunoglobulin

Abstract

Evidence that physiological control of human humoral autoimmune reactions depends, at least in part, on the formation of anti-idiotypic antibodies is accumulating. Upon binding to the corresponding idiotypes, anti-idiotypes will prevent autoantibodies from reacting with the primary antigen and/or eventually expedite removal of autoantibodies from the circulation and down-regulate their formation. In patients with autoantibodies against clotting factor VIII:C or fibrinogen, clinical improvement was associated with formation of anti-idiotypes against the autoantibodies. In addition, iv immunoglobulin (IVIg) preparations derived from plasma pools of thousands of healthy donors expressed anti-idiotypes against such autoantibodies as anti-clotting factor VIII:C, antithyroglobulin, and anti-intrinsic factor, but the specificity of the anti-idiotypes appears to be restricted for particular idiotypes. This explains why not all patients are responders to therapeutic intervention with IVIg. On one hand, definite in vitro neutralization of autoantibody activity by IVIg added in multiple proportions is not followed infallibly by in vivo response, and on the other hand, a good therapeutic effect often lasts long beyond normal half-lives of infused IVIg. The present overview compares the authors' own work with that described in recently published literature on exploring anti-idiotypy in therapy.