Human complement activation by self-associated IgG rheumatoid factors.
IgG rheumatoid factors (IgG-RFs) undergo concentration-dependent self-association into dimers and higher polymers, as previously reported. The interactions of purified IgG-RF from the plasma of 3 patients with rheumatoid arthritis, with guinea pig and human complement were studied. Self-associating IgG-RFs were isolated by affinity columns and gel filtration. These preparations contained no detectable IgM and were composed only of IgG subclasses known to fix complement. Complement utilization of IgG-RF was compared with that of monomeric IgG, heat-aggregated IgG, and soluble rabbit IgG immune complexes. Although incubation of IgG-RF or monomeric IgG with 3 units of guinea pig or human complement resulted in decreased hemolysis of sheep erythrocytes sensitized with IgM hemolysin, these substances were less than 100 times as effective as heat-aggregated IgG or soluble immune complexes. The ability of human or guinea pig complement that had been incubated with IgG-RF to restore hemolytic activity to C4-deficient guinea pig serum served to distinguish Clq binding from complement cascade activation. IgG-RFs and monomeric IgG did not activate guinea pig complement cascade in contrast to aggregated IgG. IgG-RFs, however, activated human complement cascade; monomeric IgG only bound human Clq. These results indicate that self-associated IgG-RFs can activate human complement in fluid phase, but less effectively than aggregated IgG or large-latticed immune complexes.
D001172:Arthritis, Rheumatoid / Q000097:blood; D003167:Complement Activation / Q000187:drug effects*; D003181:Complement C4 / Q000172:deficiency; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis*; D012217:Rheumatoid Factor / Q000032:analysis / Q000494:pharmacology*
D003181:Complement C4; D007074:Immunoglobulin G; D012217:Rheumatoid Factor