Effect of rheumatoid factor on complement-mediated phagocytosis.
The frequency and amount of IgM rheumatoid factor (RF) in the blood of patients with rheumatoid arthritis (RA) correlate with the severity of the disease and the number of complications. Though previous studies of RF in subacute bacterial endocarditis have shown that RF inhibits phagocytosis of microorganisms by granulocytes, the presence of low levels of complement (C) in blood and synovial fluid of patients with the highest titers of RF suggests that an interaction between RF and C may contribute to the inflammatory process in RA. We thus employed a quantitative methodology to examine the effect of RF on complement-dependent phagocytosis of sheep erythrocytes by rabbit granulocytes. Addition of 2500 molecules of IgM RF to sheep cells heavily coated with IgG antibody (195,000 molecules per cell) resulted in virtually complete inhibition of uptake of C3 (beta(1c)) and prevention of phagocytosis, an effect resulting from inhibition of uptake of C1 by the cells. When erythrocytes coated with only 34,000 molecules of IgG antibody were employed, phagocytosis was similarly inhibited. However the effect of RF on such cells was shown to be primarily mediated through inhibition of C4 rather than C1 uptake. Although the results do not exclude the participation of an IgM RF of higher avidity, present only in the tissues in rheumatoid inflammation, circulating IgM RF probably does not play a potentiating role in rheumatoid inflammation.
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001665:Binding Sites; D003168:Complement Fixation Tests; D003165:Complement System Proteins; D004912:Erythrocytes / Q000276:immunology; D006168:Guinea Pigs / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007456:Iodine Isotopes; D007962:Leukocytes / Q000276:immunology; D010587:Phagocytosis; D011817:Rabbits / Q000276:immunology; D012217:Rheumatoid Factor; D012756:Sheep / Q000276:immunology
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007456:Iodine Isotopes; D003165:Complement System Proteins; D012217:Rheumatoid Factor