Treatment with IVIg can, on rare occasions, lead to detrimental effects such as enhanced erythrocyte sequestration and an increase in serum immune complexes with inflammatory sequellae such as exacerbation of glomerular nephritis. In this study, IVIg (Sandoglobin) was examined for 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 HR separated IVIg into two fractions: monomeric IgG (74%) and larger complexes of the molecular weight of an IgG dimer or greater (≥ 300 kD) (26%). In the presence of complement, the ‘dimers’ bound to human erythrocytes, rendering them susceptible to phagocytosis in vitro. Removal of erythrocyte‐specific isoantibodies from the IVIg had no effect on ‘dimer’ binding to the erythrocytes. Monomeric IgG contained virtually no complement‐activating, erythrocyte‐binding activity. Erythrocyte binding of complement‐bearing IgG ‘dimers’ and subsequent phagocytosis resembles the binding of complement‐bearing immune complexes to erythrocyte CR1. Exposure to Factor I leads to the release of complement‐bearing IgG ‘dimers’ from erythrocyte CR1 and to the abrogation of erythrophagocytosis. Binding of complement‐bearing IgG ‘dimers’ to the erythrocyte is blocked by To5, a CR1‐specific monoclonal antibody.

Membrane alterations resulting in the binding of opsonins and the sequestration of senescent RBCs may be similar to those that occur on diamide-oxidized RBCs. They suggest the need for cooperative events among oxidation, clustering and cross-linking, and serum opsonization.

It may be desirable to remove isoantibodies from IVIg especially for anemic patients or those who respond to the IVIg with a hemolytic episode.

Background and Objectives: IVIg, while generally a safe therapy for a variety of immunological disorders, can have detrimental effects on erythrocyte (RBC) homeostasis. We studied the mediation of erythrophagocytosis by isoantibodies in IVIg. Materials and Methods: RBC were exposed to IVIg and binding of IgG determined by flow cytometry. In vitro phagocytosis of these RBC was assayed. Results: Anti–A and anti–B in IVIg mediate Fc–dependent erythrophagocytosis even in the presence of excess IVIg. Removal of these isoantibodies from IVIg prevents IgG binding and erythrophagocytosis. Complement enhances IVIg–mediated RBC sequestration. Conclusion: It may be desirable to remove isoantibodies from IVIg especially for anemic patients or those who respond to the IVIg with a hemolytic episode.