Autoantibodies purified from therapeutic preparations of intravenous immunoglobulins (IVIg) induce the formation of autoimmune complexes in normal human serum: a role in the in vivo mechanisms of action of IVIg?
Although intravenous immunoglobulins (IVIg) are widely used in the treatment of many autoimmune and inflammatory diseases, the mechanisms of action are still unclear in most cases. We have recently reported the presence of soluble autoimmune complexes (auto-IC) in human serum after the addition of a dose of IVIg similar to the one used in therapy. Here, we report the isolation and characterization of the responsible auto-IgG present in IVIg. The auto-IgG were purified by affinity chromatography on serum proteins immobilized on Sepharose. The purified auto-IgG constituted approximately 3% of the IgG present in IVIg and recognized a wide variety of structures in ELISA as well as many serum proteins on western blots. Auto-IC were formed in human serum following the addition of an amount of purified auto-IgG sufficient to over-saturate the auto-IgG inhibitory mechanisms known to be present in normal serum. These results indicate that most of the IgG present in IVIg are not involved in the formation of the soluble auto-IC, raising the possibility of preparing from IVIg a novel product which could be used for the treatment of the autoimmune diseases in which IC are thought to play an important role.
Lamoureux
Josée
J
HEMA-QUEBEC, Research and Development, 2535, Laurier Blvd, Ste-Foy, Quebec, G1V 4M3, Canada.
Aubin
Eric
E
Lemieux
Réal
R
D001323:Autoantibodies / Q000276:immunology* / Q000302:isolation & purification* / Q000627:therapeutic use; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D044967:Serum / Q000276:immunology*
D001323:Autoantibodies; D001324:Autoantigens; D016756:Immunoglobulins, Intravenous