Circulating non-immune IgG complexes in health and disease

IgG molecules possess a well-defined ability to form complexes with various proteins at interaction sites composed of residues of the constant domains. Such non-immune complexes (non-ICs) were recently identified in the circulatory system of healthy people, as well as patients suffering from various pathologies. By forming non-ICs, attached proteins that are harmful to the organism (anaphylatoxins, for example) are removed from the circulation. Non-immune IgG complexes can react simultaneously with two cell receptors—one specific for IgG, and another specific for an associated protein. Such double reactions augment cellular responses. The attachment of a protein to an IgG site may induce structural changes in neighboring areas of IgG molecules. The formation of non-ICs helps proteins with low molecular mass to escape glomerular filtration, as well as enzymatic degradation and cell uptake. Non-immune IgG complexes have been found in commercial immune globulin preparations used for the treatment of various diseases. Among the IgG-attached proteins, there are specific disease biomarkers used for clinical diagnostics and understanding disease processes. Therefore, in order to identify potential biomarkers, not only proteins that are free in the liquid phase of serum but also proteins associated with abundant proteins such as IgG must be investigated.