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. 1971 Jun;8(6):889–899.

Evidence for immune complexes containing antibody to the pepsin site of IgG in rheumatoid synovial fluids

O J Mellbye, J B Natvig
PMCID: PMC1713037  PMID: 4933318

Abstract

In seventy cases of rheumatoid arthritis, the synovial fluid to serum ratio for the titre of pepsin agglutinator, i.e. the antibody to the pepsin site of IgG, was studied. This was compared with the corresponding ratio for another antibody of the same immunoglobulin class and for other proteins. By this method there was evidence for local production of pepsin agglutinator in two cases and for local inhibition in two other cases. Density gradient ultracentrifugation, performed at pH 7·4 and 3·0, suggested that pepsin agglutinator in immune complexes was present in most of the synovial fluids containing this antibody. Complexes of pepsin agglutinator and F(ab')2 IgG, prepared in vitro, appeared to fix only small amounts of human complement. Neither did fixation of pepsin agglutinator to immune precipitates increase their complement binding activity.

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Selected References

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

  1. Art G. P., Finlayson J. S. Stability of immune serum globulin during storage: effects of prior heating. Vox Sang. 1969 Nov;17(5):419–433. doi: 10.1111/j.1423-0410.1969.tb00412.x. [DOI] [PubMed] [Google Scholar]
  2. BLAND J. H., CLARK L. Rheumatoid factor in serum and joint fluid. Ann Intern Med. 1963 May;58:829–836. doi: 10.7326/0003-4819-58-5-829. [DOI] [PubMed] [Google Scholar]
  3. FAHEY J. L., MCKELVEY E. M. QUANTITATIVE DETERMINATION OF SERUM IMMUNOGLOBULINS IN ANTIBODY-AGAR PLATES. J Immunol. 1965 Jan;94:84–90. [PubMed] [Google Scholar]
  4. FAIRLEY G. H., HARRIS G. The production of anti-human-globulin sera of different specificities in rabbits. Vox Sang. 1962;7:175–189. doi: 10.1111/j.1423-0410.1962.tb03241.x. [DOI] [PubMed] [Google Scholar]
  5. FUDENBERG H. H., KUNKEL H. G. Physical properties of the red cell agglutinins in acquired hemolytic anemia. J Exp Med. 1957 Nov 1;106(5):689–702. doi: 10.1084/jem.106.5.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. HARBOE M., RAU B., AHO K. PROPERTIES OF VARIOUS ANTI-GAMMA-GLOBULIN FACTORS IN HUMAN SERA. J Exp Med. 1965 Apr 1;121:503–519. doi: 10.1084/jem.121.4.503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Hannestad K., Mellbye O. J. Rheumatoid factor in synovial effusions: local production and consumption. Clin Exp Immunol. 1967 Jul;2(4):501–509. [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. ISHIZAKA K., ISHIZAKA T., CAMPBELL D. H. Biologic activity of soluble antigen-antibody complexes. III. J Immunol. 1959 Aug;83:105–115. [PubMed] [Google Scholar]
  11. KUNKEL H. G., TAN E. M. AUTOANTIBODIES AND DISEASE. Adv Immunol. 1964;27:351–395. doi: 10.1016/s0065-2776(08)60711-7. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Kormeier L. C., Ing J. T., Mandy W. J. Specificity of antiglobulin factors in normal human serum reacting with enzyme digested gamma-G-globulin. J Immunol. 1968 Mar;100(3):612–621. [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Lawrence T. G., Jr, Williams R. C., Jr Studies of human anti-gamma-globulin factors reacting with pepsin-digested gamma-globulins. J Exp Med. 1967 Feb 1;125(2):233–248. doi: 10.1084/jem.125.2.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mellbye O. J., Natvig J. B. Experimentally produced antibodies to the pepsin site of IgG due to untreated autologous IgG in immune complexes. Clin Exp Immunol. 1970 Aug;7(2):257–267. [PMC free article] [PubMed] [Google Scholar]
  17. Mellbye O. J. Reversible agglutination of trypsinised red cells by normal human sera: identification of the agglutinating factor as a gamma-M-globulin. Scand J Haematol. 1965;2(4):318–330. doi: 10.1111/j.1600-0609.1965.tb01308.x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Müller-Eberhard H. J. Complement. Annu Rev Biochem. 1969;38:389–414. doi: 10.1146/annurev.bi.38.070169.002133. [DOI] [PubMed] [Google Scholar]
  20. Natvig J. B. Heterogeneity of anti-gamma-globulin factors detected by pepsin-digested human gamma G-globulin. Acta Pathol Microbiol Scand. 1966;66(3):369–382. doi: 10.1111/apm.1966.66.3.369. [DOI] [PubMed] [Google Scholar]
  21. Natvig J. B. Human anti-gamma-globulin antibodies specific for gamma G heavy chain subclasses. Immunology. 1970 Jul;19(1):125–135. [PMC free article] [PubMed] [Google Scholar]
  22. OSTERLAND C. K., HARBOE M., KUNKEL H. G. Anti-gamma-globulin factors in human sera revealed by enzymatic splitting of anti-Rh antibodies. Vox Sang. 1963 Mar-Apr;8:133–152. doi: 10.1111/j.1423-0410.1963.tb03290.x. [DOI] [PubMed] [Google Scholar]
  23. RODNAN G. P., EISENBEIS C. H., Jr, CREIGHTON A. S. THE OCCURRENCE OF RHEUMATOID FACTOR IN SYNOVIAL FLUID. Am J Med. 1963 Aug;35:182–188. doi: 10.1016/0002-9343(63)90209-2. [DOI] [PubMed] [Google Scholar]
  24. SCHUR P. H., BECKER E. L. PEPSIN DIGESTION OF RABBIT AND SHEEP ANTIBODIES. THE EFFECT ON COMPLEMENT FIXATION. J Exp Med. 1963 Dec 1;118:891–904. doi: 10.1084/jem.118.6.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schoenfeld L. S., Epstein W. V. Macroglobulin rheumatoid factors directed toward buried antigenic sites of human gamma-globulins. Vox Sang. 1965 Jul-Aug;10(4):482–492. doi: 10.1111/j.1423-0410.1965.tb04361.x. [DOI] [PubMed] [Google Scholar]
  26. Tönder O., Milgrom F. Studies on agglutination by macromolecular antibodies. I. Agglutination of rabbit erythrocytes by human sera. Vox Sang. 1965 Nov-Dec;10(6):708–720. doi: 10.1111/j.1423-0410.1965.tb05182.x. [DOI] [PubMed] [Google Scholar]
  27. Wilson I. D., Soltis R. D., Williams R. C., Jr Naturally occurring human antibodies to pepsin-digested IgA. Blood. 1970 Sep;36(3):390–398. [PubMed] [Google Scholar]
  28. Winchester R. J., Agnello V., Kunkel H. G. The joint-fluid gammaG-globulin complexes and their relationship to intraarticular complement dimunition. Ann N Y Acad Sci. 1969 Dec 10;168(1):195–203. doi: 10.1111/j.1749-6632.1969.tb43108.x. [DOI] [PubMed] [Google Scholar]
  29. 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]

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