Abstract
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.