IMMUNE COMPLEX-LIKE MOIETIES IN IMMUNOGLOBULIN FOR INTRAVENOUS USE (IVIG) BIND COMPLEMENT AND ENHANCE PHAGOCYTOSIS OF HUMAN ERYTHROCYTES

Treatment with IVIg can, on rare occasions, lead to detrimental effect s such as enhanced erythrocyte sequestration and an increase in serum immune complexes with inflammatory sequellae such as exacerbation of g lomerular nephritis. In this study, IVIg (Sandoglobin) was examined fo r complement binding moieties which resemble immune complexes and can mediate the binding of IgG and C'3b to human erythrocytes via CR1 and enhance erythrocyte susceptibility to sequestration. Sephacryl S-200 H R separated IVIg into two fractions: monomeric IgG (74%) and larger co mplexes of the molecular weight of an IgG dimer or greater (greater th an or equal to 300 kD) (26%). In the presence of complement, the 'dime rs' bound to human erythrocytes, rendering them susceptible to phagocy tosis in vitro. Removal of erythrocyte-specific isoantibodies from the IVIg had no effect on 'dimer' binding to the erythrocytes. Monomeric complement-bearing IgG 'dimers' and subsequent phagocytosis resembles the binding of complement-bearing immune complexes to erythrocyte CR1. Exposure to Factor 1 leads to the release of complement-bearing IgG ' dimers' from erythrocyte CR1 and to the abrogation of erythrophagocyto sis. Binding of complement-bearing IgG 'dimers' to the erythrocyte is blocked by To5, a CR1-specific monoclonal antibody.