Immune complex-like moieties in immunoglobulin for intravenous use (i.v.Ig) bind complement and enhance phagocytosis of human erythrocytes.
Treatment with i.v.Ig 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, i.v.Ig (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 i.v.Ig into two fractions: monomeric IgG (74%) and larger complexes of the molecular weight of an IgG dimer or greater (> or = 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 i.v.Ig 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.
Department of Immunology, Rappaport Faculty of Medicine, Technion, Haifa, Israel.
H
H
Shoham-Kessary
Y
Y
Naot
H
H
Gershon
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D003179:Complement C3b / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D019281:Dimerization; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D016756:Immunoglobulins, Intravenous / Q000378:metabolism*; D066298:In Vitro Techniques; D007518:Isoantibodies / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010587:Phagocytosis; D017463:Receptors, Complement 3b / Q000276:immunology
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007518:Isoantibodies; D017463:Receptors, Complement 3b; D003179:Complement C3b; D005340:Fibrinogen; D003165:Complement System Proteins