Abstract
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 (β1c) 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.
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- AHO K., HARBOE M., LEIKOLA J. STUDIES OF THE ANTIBODY NATURE OF THE RHEUMATOID FACTOR. REACTION OF THE RHEUMATOID FACTOR WITH SHEEP ERYTHROCYTES SENSITIZED WITH HUMAN ANTI-SHEEP CELL ANTIBODIES AND WITH O RH POSITIVE CELLS SENSITIZED WITH INCOMPLETE ANTI-RH ANTIBODIES. Immunology. 1964 Jul;7:403–418. [PMC free article] [PubMed] [Google Scholar]
- Berken A., Benacerraf B. Properties of antibodies cytophilic for macrophages. J Exp Med. 1966 Jan 1;123(1):119–144. doi: 10.1084/jem.123.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blondin C., McDuffie F. C. Role of IgG and IgM antinuclear antibodies in formation of lupus erythematosus cells and extracellular material. Arthritis Rheum. 1970 Nov-Dec;13(6):786–797. doi: 10.1002/art.1780130608. [DOI] [PubMed] [Google Scholar]
- Borsos T., Rapp H. J. Hemolysin titration based on fixation of the activated first component of complement: evidence that one molecule of hemolysin suffices to sensitize an erythrocyte. J Immunol. 1965 Sep;95(3):559–566. [PubMed] [Google Scholar]
- Ewald R. W., Schubart A. F. Agglutinating activity of the complement component C'1q in the F-II latex fixation test. J Immunol. 1966 Jul;97(1):100–105. [PubMed] [Google Scholar]
- Frank M. M., Gaither T. Evidence that rabbit gamma G haemolysin in capable of utilizing guinea-pig complement more efficiently than rabbit gamma M haemolysin. Immunology. 1970 Dec;19(6):975–981. [PMC free article] [PubMed] [Google Scholar]
- Gigli I., Nelson R. A., Jr Complement dependent immune phagocytosis. I. Requirements for C'1, C'4, C'2, C'3. Exp Cell Res. 1968 Jul;51(1):45–67. doi: 10.1016/0014-4827(68)90158-4. [DOI] [PubMed] [Google Scholar]
- Golden H. E., McDuffie F. C. Role of lupus erythematosus factor and accessory serum factors in production of extracellular nuclear material. Ann Intern Med. 1967 Oct;67(4):780–790. doi: 10.7326/0003-4819-67-4-780. [DOI] [PubMed] [Google Scholar]
- HEIMER R., LEVIN F. M., KAHN M. F. INHIBITION OF COMPLEMENT FIXATION BY HUMAN SERUM. II. THE ACTIVITY OF A GAMMA-LM GLOBULIN AND RHEUMATOID FACTOR IN COMPLEMENT FIXATION REACTIONS. J Immunol. 1963 Dec;91:866–872. [PubMed] [Google Scholar]
- HEIMER R., WOODS K. R., ENGLE R. L., Jr Amino acid analyses of rheumatoid factors and normal gammaglobulins. Proc Soc Exp Biol Med. 1962 Jul;110:496–500. doi: 10.3181/00379727-110-27562. [DOI] [PubMed] [Google Scholar]
- HOLLANDER J. L., MCCARTY D. J., Jr, ASTORGA G., CASTRO-MURILLO E. STUDIES ON THE PATHOGENESIS OF RHEUMATOID JOINT INFLAMMATION. I. THE "R.A. CELL" AND A WORKING HYPOTHESIS. Ann Intern Med. 1965 Feb;62:271–280. doi: 10.7326/0003-4819-62-2-271. [DOI] [PubMed] [Google Scholar]
- Hunder G. G., McDuffie F. C., Hepper N. G. Pleural fluid complement in systemic lupus erythematosus and rheumatoid arthritis. Ann Intern Med. 1972 Mar;76(3):357–363. doi: 10.7326/0003-4819-76-3-357. [DOI] [PubMed] [Google Scholar]
- Linscott W. D. Complement fixation: the effects of IgG and IgM antibody concentration on C1-binding affinity. J Immunol. 1970 Oct;105(4):1013–1023. [PubMed] [Google Scholar]
- MUELLER-EBERHARD H. J., BIRO C. E. ISOLATION AND DESCRIPTION OF THE FOURTH COMPONENT OF HUMAN COMPLEMENT. J Exp Med. 1963 Sep 1;118:447–466. doi: 10.1084/jem.118.3.447. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MULLER-EBERHARD H. J., NILSSON U., ARONSSON T. Isolation and characterization of two beta1-glycoproteins of human serum. J Exp Med. 1960 Feb 1;111:201–215. doi: 10.1084/jem.111.2.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- MacKenzie M. R., Creevy N., Heh M. The interaction of human IgM and C1q. J Immunol. 1971 Jan;106(1):65–68. [PubMed] [Google Scholar]
- McConahey P. J., Dixon F. J. A method of trace iodination of proteins for immunologic studies. Int Arch Allergy Appl Immunol. 1966;29(2):185–189. doi: 10.1159/000229699. [DOI] [PubMed] [Google Scholar]
- Messner R. P., Jelinek J. Receptors for human gamma G globulin on human neutrophils. J Clin Invest. 1970 Dec;49(12):2165–2171. doi: 10.1172/JCI106435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Messner R. P., Laxidal T., Quie P. G., Williams R. C., Jr Serum opsonin, bacteria, and polymorphonuclear leukocyte interactions in subacute bacterial endocarditis. Anti-gamma-globulin factors and their interaction with specific opsonins. J Clin Invest. 1968 May;47(5):1109–1120. doi: 10.1172/JCI105800. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller-Eberhard H. J., Polley M. J., Calcott M. A. Formation and functional significance of a molecular complex derived from the second and the fourth component of human complement. J Exp Med. 1967 Feb 1;125(2):359–380. doi: 10.1084/jem.125.2.359. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müllerèberhard H. J., Dalmasso A. P., Calcott M. A. The reaction mechanism of beta-1C-globulin (C'3) in immune hemolysis. J Exp Med. 1966 Jan 1;123(1):33–54. doi: 10.1084/jem.123.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NELSON R. A., Jr The immune-adherence phenomenon; an immunologically specific reaction between microorganisms and erythrocytes leading to enhanced phagocytosis. Science. 1953 Dec 18;118(3077):733–737. doi: 10.1126/science.118.3077.733. [DOI] [PubMed] [Google Scholar]
- NILSSON U. R., MUELLER-EBERHARD H. J. ISOLATION OF BETA IF-GLOBULIN FROM HUMAN SERUM AND ITS CHARACTERIZATION AS THE FIFTH COMPONENT OF COMPLEMENT. J Exp Med. 1965 Aug 1;122:277–298. doi: 10.1084/jem.122.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nelson R. A., Jr, Jensen J., Gigli I., Tamura N. Methods for the separation, purification and measurement of nine components of hemolytic complement in guinea-pig serum. Immunochemistry. 1966 Mar;3(2):111–135. doi: 10.1016/0019-2791(66)90292-8. [DOI] [PubMed] [Google Scholar]
- Onoue K., Tanigaki N., Yagi Y., Pressman D. IgM and IgG anti-hapten antibody: hemolytic, hemagglutinating and precipitating activity. Proc Soc Exp Biol Med. 1965 Nov;120(2):340–346. doi: 10.3181/00379727-120-30531. [DOI] [PubMed] [Google Scholar]
- RESTIFO R. A., LUSSIER A. J., RAWSON A. J., ROCKEY J. H., HOLLANDER J. L. STUDIES ON THE PATHOGENESIS OF RHEUMATOID JOINT INFLAMMATION. 3. THE EXPERIMENTAL PRODUCTION OF ARTHRITIS BY THE INTRA-ARTICULAR INJECTION OF PURIFIED 7S GAMMA GLOBULIN. Ann Intern Med. 1965 Feb;62:285–291. doi: 10.7326/0003-4819-62-2-285. [DOI] [PubMed] [Google Scholar]
- ROBBINS J. B., KENNY K., SUTER E. THE ISOLATION AND BIOLOGICAL ACTIVITIES OF RABBIT GAMMA M- AND GAMMA G-ANTI-SALMONELLA TYPHIMURIUM ANTIBODIES. J Exp Med. 1965 Aug 1;122:385–402. doi: 10.1084/jem.122.2.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rowley D., Turner K. J. Number of molecules of antibody required to promote phagocytosis of one bacterium. Nature. 1966 Apr 30;210(5035):496–498. doi: 10.1038/210496a0. [DOI] [PubMed] [Google Scholar]
- Schmid F. R., Roitt I. M., Rocha M. J. Complement fixation by a two-component antibody system: immunoglobulin G and immunoglobulin M anti-globulin (rheumatoid factor). Parodoxical effect related to immunoglobulin G concentration. J Exp Med. 1970 Oct 1;132(4):673–693. doi: 10.1084/jem.132.4.673. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sliwinski A. J., Zvaifler N. J. The removal of aggregated and nonaggregated autologous gamma globulin from rheumatoid joints. Arthritis Rheum. 1969 Oct;12(5):504–514. doi: 10.1002/art.1780120507. [DOI] [PubMed] [Google Scholar]
- Willoughby W. F., Mayer M. M. Antibody-complement complexes. Science. 1965 Nov 12;150(3698):907–908. doi: 10.1126/science.150.3698.907. [DOI] [PubMed] [Google Scholar]
- Winchester R. J., Agnello V., Kunkel H. G. Gamma globulin complexes in synovial fluids of patients with rheumatoid arthritis. Partial characterization and relationship to lowered complement levels. Clin Exp Immunol. 1970 May;6(5):689–706. [PMC free article] [PubMed] [Google Scholar]
- Zvaifler N. J., Schur P. Reactions of aggregated mercaptoethanol treated gamma globulin with rheumatoid factor--precipitin and complement fixation studies. Arthritis Rheum. 1968 Aug;11(4):523–536. doi: 10.1002/art.1780110402. [DOI] [PubMed] [Google Scholar]