Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1975 Aug;56(2):458–466. doi: 10.1172/JCI108112

Immune complexes in sera and synovial fluids of patients with rheumatoid arthritis. Radioimmunoassay with monocylonal rheumatoid factor.

H S Luthra, F C McDuffie, G G Hunder, E A Samayoa
PMCID: PMC436606  PMID: 125289

Abstract

Evidence for the presence of immune complexes in blood, synovial fluid, and tisues of patients with rheumatoid arthritis (RA) includes low complement levels in blood and effusions, deposition of immunoreactants in tissues and vessel walls, precipitate formation after addition of monoclonal rheumatoid factor (mRF) to serum or synovial fluid. To quantitate immune complex-like material in RA patients, we developed a radioimmunoassay based on inhibition by test samples of the interaction of (125I)aggregated IgG (agg IgG) and mRF coupled to cellulose. This method could measure immune complexes of human antibody with hemocyanine prepared in vitro. The assay was not influenced by presence of polyclonal RF in test samples, nor by freezing and thawing. Normal levels of immune complex-like material in serum were less than 25 mug agg IgG EQ/ML. 12 of 51 RA sera examined (26%) contained more than 25 mug/ml. The presence of this material in RA sera was found to correlate with severity of disease, as measured by anatomical stage and functional class. There was an inverse correlation of the material with serum C4 level. Rheumatoid synovial fluids generally contained higher levels than serum, and five of 23 contained very much higher levels. The frequency of elevated levels of immune complex-like material in sera of patients with systemic lupus erythematosus (2 of 29) and with miscellaneous vasculitides (2 of 21 was much lower than in RA, suggesting that mRF exhibits a specificity for only certain kinds of immune complexes. The reason for this apparent specificity may explain such distinctive features of RA as the high frequency of polyclonal RF, the lack of immune complex nephritis, and the generally normal levels of serum complement.

Full text

PDF
458

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agnello V., Koffler D., Eisenberg J. W., Winchester R. J., Kundel H. G. C1g precipitins in the sera of patients with systemic lupus erythematosus and other hypocomplementemic states: characterization of high and low molecular weight types. J Exp Med. 1971 Sep 1;134(3 Pt 2):228s–241s. [PubMed] [Google Scholar]
  2. Axén R., Porath J., Ernback S. Chemical coupling of peptides and proteins to polysaccharides by means of cyanogen halides. Nature. 1967 Jun 24;214(5095):1302–1304. doi: 10.1038/2141302a0. [DOI] [PubMed] [Google Scholar]
  3. Baumal R., Broder I. Studies into the occurrence of soluble antigen-antibody complexes in disease. 3. Rheumatoid arthritis and other human diseases. Clin Exp Immunol. 1968 Jul;3(6):555–569. [PMC free article] [PubMed] [Google Scholar]
  4. CHRISTIAN C. L. Characterization of the reactant (gamma globulin factor) in the F II precipitin reaction and the F II tanned sheep cell agglutination test. J Exp Med. 1958 Jul 1;108(1):139–157. doi: 10.1084/jem.108.1.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conn D. L., McDuffie F. C., Dyck P. J. Immunopathologic study of sural nerves in rheumatoid arthritis. Arthritis Rheum. 1972 Mar-Apr;15(2):135–143. doi: 10.1002/art.1780150202. [DOI] [PubMed] [Google Scholar]
  6. Cowdery J. S., Jr, Treadwell P. E., Fritz R. B. A radioimmunoassay for human antigen-antibody complexes in clinical material. J Immunol. 1975 Jan;114(1 Pt 1):5–9. [PubMed] [Google Scholar]
  7. FRANKLIN E. C., HOLMAN H. R., MULLER-EBERHARD H. J., KUNKEL H. G. An unusual protein component of high molecular weight in the serum of certain patients with rheumatoid arthritis. J Exp Med. 1957 May 1;105(5):425–438. doi: 10.1084/jem.105.5.425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Franco A. E., Schur P. H. Hypocomplementemia in rheumatoid arthritis. Arthritis Rheum. 1971 Mar-Apr;14(2):231–238. doi: 10.1002/art.1780140206. [DOI] [PubMed] [Google Scholar]
  9. Gordon D. A., Bell D. A., Baumal R., Broder I. Studies into the occurrence of soluble antigen-antibody complexes in disease. IV. Correlation between the rheumatoid biologically active factor and the clinical features of rheumatoid arthritis. Clin Exp Immunol. 1969 Jul;5(1):57–66. [PMC free article] [PubMed] [Google Scholar]
  10. HEDBERG H. STUDIES ON THE DEPRESSED HEMOLYTIC COMPLEMENT ACTIVITY OF SYNOVIAL FLUID IN ADULT RHEUMATOID ARTHRITIS. Acta Rheumatol Scand. 1963;9:165–193. [PubMed] [Google Scholar]
  11. Hannestad K. Presence of aggregated gamma-G-globulin in certain rheumatoid synovial effusions. Clin Exp Immunol. 1967 Jul;2(4):511–529. [PMC free article] [PubMed] [Google Scholar]
  12. Hannestad K. Rheumatoid factors reacting with autologous native gamma-G-globulin and joint fluid gamma-G aggregates. Clin Exp Immunol. 1968 Sep;3(7):671–690. [PMC free article] [PubMed] [Google Scholar]
  13. Hunder G. G., McDuffie F. C. Hypocomplementemia in rheumatoid arthritis. Am J Med. 1973 Apr;54(4):461–472. doi: 10.1016/0002-9343(73)90042-9. [DOI] [PubMed] [Google Scholar]
  14. KUNKEL H. G., MULLER-EBERHARD H. J., FUDENBERG H. H., TOMASI T. B. Gamma globulin complexes in rheumatoid arthritis and certain other conditions. J Clin Invest. 1961 Jan;40:117–129. doi: 10.1172/JCI104224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  16. Normansell D. E., Stanworth D. R. Ultracentrifugal studies of the reactions of rheumatoid factor with native human gamma-G-globulin. Immunology. 1966 Jun;10(6):527–533. [PMC free article] [PubMed] [Google Scholar]
  17. Nydegger U. E., Lambert P. H., Gerber H., Miescher P. A. Circulating immune complexes in the serum in systemic lupus erythematosus and in carriers of hepatitis B antigen. Quantitation by binding to radiolabeled C1q. J Clin Invest. 1974 Aug;54(2):297–309. doi: 10.1172/JCI107765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. PEKIN T. J., Jr, ZVAIFLER N. J. HEMOLYTIC COMPLEMENT IN SYNOVIAL FLUID. J Clin Invest. 1964 Jul;43:1372–1382. doi: 10.1172/JCI105013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
  20. Rodman W. S., Williams R. C., Jr, Bilka P. J., Müller-Eberhard H. J. Immunofluorescent localization of the third and the fourth component of complement in synovial tissue from patients with rheumatoid arthritis. J Lab Clin Med. 1967 Jan;69(1):141–150. [PubMed] [Google Scholar]
  21. Russell M. L., Gordon D. A., BRoder I. Studies into the occurrence of soluble antigen-antibody complexes in disease. VII. Clinical-laboratory correlations of immunoglobulin complexes in rheumatoid synovial fluid. J Rheumatol. 1974 Jun;1(2):153–158. [PubMed] [Google Scholar]
  22. Theofilopoulos A. N., Wilson C. B., Bokisch V. A., Dixon F. J. Binding of soluble immune complexes to human lymphoblastoid cells. II. Use of Raji cells to detect circulating immune complexes in animal and human sera. J Exp Med. 1974 Nov 1;140(5):1230–1244. doi: 10.1084/jem.140.5.1230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Urowitz M. B., Gordon D. A., Broder I. Studies into the occurrence of soluble antigen-antibody complexes in disease. V. Second assessment of correlation between the rheumatoid biologically active factor (RBAF) and the clinical features of rheumatoid arthritis. Arthritis Rheum. 1973 Mar-Apr;16(2):225–230. doi: 10.1002/art.1780160214. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Winchester R. J., Kunkel H. G., Agnello V. Occurrence of -globulin complexes in serum and joint fluid of rheumatoid arthritis patients: use of monoclonal rheumatoid factors as reagents for their demonstration. J Exp Med. 1971 Sep 1;134(3 Pt 2):286s–295s. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES