Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1977 May;59(5):862–868. doi: 10.1172/JCI108708

Circulating complement breakdown products in patients with rheumatoid arthritis. Correlation between plasma C3d, circulating immune complexes, and clinical activity.

U E Nydegger, R H Zubler, R Gabay, G Joliat, C H Karagevrekis, P H Lambert, P A Miescher
PMCID: PMC372294  PMID: 853126

Abstract

Quantitative determination of the small C3 breakdown product, C3d, was used to investigate complement activation in 45 plasma samples from 30 patients with rheumatoid arthritis (RA). The mean plasma C3e level in these samples (3.0 +/- 1.3 mg/100 ml) was significantly increased (P less than 0.001) as compared to patients with degenerative joint disease (0.9 +/- 0.4 mg/100 ml) and healthy blood donors (0.8 +/- 0.5 mg/100 ml). C3d levels were increased by more than s SD in 79% of RA samples. Plasma C3d levels were compared with C3d concentrations in synovial fluid. In most RA patients, the C3d levels were higher in synovial fluid than in plasma. A very significant correlation between plasma C3d levels and circulating immune complexes, as measured by determination of Clq binding activity (Clq BA), was observed (P less than 0.001). C3d levels were more elevated in RA patients with extra-articular disease manifestations (3.8 +/- 1.2 mg/100 ml) as compared to patients with joint disease alone (2.2 +/- 1.0 mg/100 ml). C3d levels and Clq BA were also significantly correlated (P less than 0.001) with the RA disease activity expressed by an index derived from sedimentation rate, joint score, and duration of morning stiffness. A close relationship between C3d levels, Clq BA, and the clinical activity further appeared during follow-up studies. The present observations suggest that a parallel but rather independent activation of the complement system may be induced by immune complexes in circulating blood and in the joint spaces during the course of rheumatoid arthritis.

Full text

PDF
864

Selected References

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

  1. Agnello V., Winchester R. J., Kunkel H. G. Precipitin reactions of the C1q component of complement with aggregated gamma-globulin and immune complexes in gel diffusion. Immunology. 1970 Dec;19(6):909–919. [PMC free article] [PubMed] [Google Scholar]
  2. Charlesworth J. A., Williams D. G., Sherington E., Lachmann P. J., Peters D. K. Metabolic studies of the third component of complement and the glycine-rich beta glycoprotein in patients with hypocomplementemia. J Clin Invest. 1974 Jun;53(6):1578–1587. doi: 10.1172/JCI107708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Conn D. L., Schroeter A. L., McDuffie F. C. Cutaneous vessel immune deposits in rheumatoid arthritis. Arthritis Rheum. 1976 Jan-Feb;19(1):15–20. doi: 10.1002/art.1780190102. [DOI] [PubMed] [Google Scholar]
  4. Gitlin J. D., Rosen F. S., Lachmann P. J. The mechanism of action of the C3b inactivator (conglutinogen-activating factor) on its naturally occurring substrate, the major fragment of the third component of complement (C3b). J Exp Med. 1975 May 1;141(5):1221–1226. doi: 10.1084/jem.141.5.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Kinsella T. D., Baum J., Ziff M. Immunofluorescent demonstration of an IgG-B1C complex in synovial lining cells of rheumatoid synovial membrane. Clin Exp Immunol. 1969 Feb;4(2):265–271. [PMC free article] [PubMed] [Google Scholar]
  7. Lachmann P. J., Müller-Eberhard H. J. The demonstration in human serum of "conglutinogen-activating factor" and its effect on the third component of complement. J Immunol. 1968 Apr;100(4):691–698. [PubMed] [Google Scholar]
  8. Lambert P. H., Nydegger U. E., Perrin L. H., McCormic J., Fehr K., Miescher P. A. Complement activation in seropositive and seronegative rheumatoid arthritis. 125I-C1q binding capacity and complement breakdown products in serum and synovial fluid. Rheumatology. 1975;6:52–59. [PubMed] [Google Scholar]
  9. Munthe E., Natvig J. B. Characterization of IgG complexes in eluates from rheumatoid tissue. Clin Exp Immunol. 1971 Feb;8(2):249–262. [PMC free article] [PubMed] [Google Scholar]
  10. Nydegger U. E., Achermann L. M., Lambert P. H., Miescher P. A. A simple automated method for complement estimation in a continuous flow system. J Immunol. 1972 Oct;109(4):910–913. [PubMed] [Google Scholar]
  11. Perrin L. H., Lambert P. H., Miescher P. A. Complement breakdown products in plasma from patients with systemic lupus erythematosus and patients with membranoproliferative or other glomerulonephritis. J Clin Invest. 1975 Jul;56(1):165–176. doi: 10.1172/JCI108065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Perrin L. H., Lambert P. H., Nydegger U. E., Miescher P. A. Quantitation of C3PA (properdin factor B) and other complement components in diseases associated with a low C3 level. Clin Immunol Immunopathol. 1973 Nov;2(1):16–27. doi: 10.1016/0090-1229(73)90032-9. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Ruddy S., Austen K. F. The complement system in rheumatoid synovitis. I. An analysis of complement component activities in rheumatoid synovial fluids. Arthritis Rheum. 1970 Nov-Dec;13(6):713–723. doi: 10.1002/art.1780130601. [DOI] [PubMed] [Google Scholar]
  15. Ruddy S., Colten H. R. Rheumatoid arthritis. Biosynthesis of complement proteins by synovial tissues. N Engl J Med. 1974 Jun 6;290(23):1284–1288. doi: 10.1056/NEJM197406062902304. [DOI] [PubMed] [Google Scholar]
  16. Ruddy S., Fearon D. T., Austen K. F. Depressed synovial fluid levels of properdin and properdin factor B in patients with rheumatoid arthritis. Arthritis Rheum. 1975 Jul-Aug;18(4):289–295. doi: 10.1002/art.1780180401. [DOI] [PubMed] [Google Scholar]
  17. Schur P. H., Austen K. F. Complement in human disease. Annu Rev Med. 1968;19:1–24. doi: 10.1146/annurev.me.19.020168.000245. [DOI] [PubMed] [Google Scholar]
  18. VAUGHAN J. H., BAYLES T. B., FAVOUR C. B. Serum complement in rheumatoid arthritis. Am J Med Sci. 1951 Aug;222(2):186–192. [PubMed] [Google Scholar]
  19. Versey J. M., Hobbs J. R., Holt P. J. Complement metabolism in rheumatoid arthritis. I. Longitudinal studies. Ann Rheum Dis. 1973 Nov;32(6):557–564. doi: 10.1136/ard.32.6.557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Weinstein A., Peters K., Brown D., Bluestone R. Metabolism of the third component of complement (C3) in patients with rheumatoid arthritis. Arthritis Rheum. 1972 Jan-Feb;15(1):49–56. doi: 10.1002/art.1780150108. [DOI] [PubMed] [Google Scholar]
  21. Whaley K., Canesi B., Moseley A., Morrow W., Sturrock R., Mitchell W., Dick W. C. Complement metabolism in the seronegative arthritides. Ann Rheum Dis. 1974 Nov;33(6):495–499. doi: 10.1136/ard.33.6.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Zubler R. H., Lange G., Lambert P. H., Miescher P. A. Detection of immune complexes in unheated sera by modified 125I-Clq binding test. Effect of heating on the binding of Clq by immune complexes and application of the test to systemic lupus erythematosus. J Immunol. 1976 Jan;116(1):232–235. [PubMed] [Google Scholar]
  24. Zubler R. H., Nydegger U., Perrin L. H., Fehr K., McCormick J., Lambert P. H., Miescher P. A. Circulating and intra-articular immune complexes in patients with rheumatoid arthritis. Correlation of 125I-Clq binding activity with clinical and biological features of the disease. J Clin Invest. 1976 May;57(5):1308–1319. doi: 10.1172/JCI108399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Zvaifler N. J. Breakdown products of C 3 in human synovial fluids. J Clin Invest. 1969 Aug;48(8):1532–1542. doi: 10.1172/JCI106119. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES