Autoantibody-induced formation of immune complexes in normal human serum

Intravenous immunoglobulins (IVIg) are concentrated preparations of purified human plasma-derived IgG routinely used in the treatment of many autoimmune diseases. Their precise mechanisms of therapeutic action have remained unclear in most diseases and are attracting much interest due to the rapidly increasing use of this precious plasma-derived product. The presence in IVIg of IgG reactive with various human structures has been known for many years. In this review, we first briefly discuss the formation and role of natural autoreactive human IgG in healthy individuals. A role for IgG autoantibodies in the in vivo immunomodulatory effects of IVIg has been proposed several years ago but the underlying mechanism has remained unclear. Recent work has shown that the large IVIg doses infused in many patients could oversaturate the normal anti-idiotype-dependent inhibition of autoreactive IgG present in the plasma of all healthy individuals since the formation of autoimmune complexes could be observed in normal serum in presence of therapeutic amounts of IVIg. These autoimmune complexes could have potent in vivo immunomodulatory effects by interacting with various IgG and complement receptors. Furthermore the autoreactive IgG can be easily purified from IVIg by affinity chromatography, raising the interesting possibility of further fractionating IVIg into different sub-products for use in the treatment of different diseases. These results indicate that natural autoantibodies have important in vivo roles not only for the protection of the body against infectious agents but also for the efficiency of passive immunotherapy procedures used in the treatment of many diseases.