Complement fixation by rheumatoid factor.
The capacity for fixation and activation of hemolytic complement by polyclonal IgM rheumatoid factors (RF) isolated from sera of patients with rheumatoid arthritis and monoclonal IgM-RF isolated from the cryoprecipitates of patients with IgM-IgG mixed cryoglobulinemia was examined. RF mixed with aggregated, reduced, and alkylated human IgG (Agg-R/A-IgG) in the fluid phase failed to significantly reduce the level of total hemolytic complement, CH50, or of individual complement components, C1, C2, C3, and C5. However, sheep erythrocytes (SRC) coated with Agg-R/A-IgG or with reduced and alkylated rabbit IgG anti-SRC antibody were hemolyzed by complement in the presence of polyclonal IgM-RF. Human and guinea pig complement worked equally well. The degree of hemolysis was in direct proportion to the hemagglutination titer of the RF against the same coated cells. Monoclonal IgM-RF, normal human IgM, and purified Waldenström macroglobulins without antiglobulin activity were all inert. Hemolysis of coated SRC by RF and complement was inhibited by prior treatment of the complement source with chelating agents, hydrazine, cobra venom factor, specific antisera to C1q, CR, C5, C6, or C8, or by heating at 56 degrees C for 30 min. Purified radiolabeled C4, C3, and C8 included in the complement source were bound to hemolysed SRC in direct proportion to the degree of hemolysis. These data indicate that polyclonal IgM-RF fix and activate complement via the classic pathway. The system described for assessing complement fixation by isolated RF is readily adaptable to use with whole human serum.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001796:Blood Protein Disorders / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D003168:Complement Fixation Tests; D003450:Cryoglobulins; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006041:Goats / Q000276:immunology; D006168:Guinea Pigs / Q000276:immunology; D006386:Hemagglutination Tests; D006461:Hemolysis; D006801:Humans; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011817:Rabbits / Q000276:immunology; D012217:Rheumatoid Factor; D012756:Sheep / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D003450:Cryoglobulins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D012217:Rheumatoid Factor