Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1971 Feb;50(2):282–293. doi: 10.1172/JCI106493

The occurrence of cryoproteins in synovial fluid; the association of a complement-fixing activity in rheumatoid synovial fluid with cold-precipitable protein

Robert L Marcus 1,2, Alexander S Townes 1,2
PMCID: PMC291922  PMID: 4992991

Abstract

A significant portion of a complement-fixing activity found in the synovial fluid of patients with rheumatoid arthritis, and previously implicated as a possible cause of the low synovial fluid complement levels in these patients behaves as a high solubility cryoprotein. Analysis of rheumatoid synovial fluid cryoproteins has revealed mixed immunoglobulins, bound complement components, fibrinogen, DNA, and rheumatoid factor.

Sorbitol density gradient studies on whole synovial fluid before and after removal of this activity has shown that the complement-fixing activity migrates in the 19S and heavier regions and that portion is removed with cryoprecipitation. Cryoproteins found in nonrheumatoid synovial fluid are generally devoid of complement-fixing activity and predominantly contain fibrinogen. DNA and IgG are also present, with IgG occurring significantly less frequently than in rheumatoid cryoproteins. These findings are discussed in relationship to recent studies demonstrating the presence of complement-fixing antibody to denatured DNA in rheumatoid cryoproteins.

Full text

PDF
282

Images in this article

289Image
on p.289

Selected References

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

  1. 1958 REVISION of diagnostic criteria for rheumatoid arthritis. Arthritis Rheum. 1959 Feb;2(1):16–20. doi: 10.1002/1529-0131(195902)2:1<16::aid-art1780020104>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  2. BECKER E. L. Concerning the mechanism of complement action. V. The early steps in immune hemolysis. J Immunol. 1960 Mar;84:299–308. [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. Broder I., Baumal R., Gordon D., Bell D. Histamine-releasing activity of rheumatoid and nonrheumatoid serum and synovial fluid. Ann N Y Acad Sci. 1969 Dec 10;168(1):126–139. doi: 10.1111/j.1749-6632.1969.tb43102.x. [DOI] [PubMed] [Google Scholar]
  5. CHRISTIAN C. L., HATFIELD W. B., CHASE P. H. Systemic lupus erythematosus. Cryoprecipitation of sera. J Clin Invest. 1963 Jun;42:823–829. doi: 10.1172/JCI104774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CHRISTIAN C. L. Studies of aggregated gamma-globulin. II. Effect in vivo. J Immunol. 1960 Jan;84:117–121. [PubMed] [Google Scholar]
  7. CRAIG J. M., GITLIN D., JANEWAY J. A. Studies on the nature of fibrinoid in the collagen diseases. Am J Pathol. 1957 Jan-Feb;33(1):55–77. [PMC free article] [PubMed] [Google Scholar]
  8. Cochrane C. G., Müller-Eberhard H. J. The derivation of two distinct anaphylatoxin activities from the third and fifth components of human complement. J Exp Med. 1968 Feb 1;127(2):371–386. doi: 10.1084/jem.127.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DEICHER H. R., HOLMAN H. R., KUNKEL H. G. The precipitin reaction between DNA and a serum factor in systemic lupus erythematosus. J Exp Med. 1959 Jan 1;109(1):97–114. doi: 10.1084/jem.109.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. FAHEY J. L., McCOY P. F., GOULIAN M. Chromatography of serum proteins in normal and pathologic sera: the distribution of protein-bound carbohydrate and cholesterol, siderophilin, thyroxin-binding protein, B12-binding protein, alkaline and acid phosphatases, radio-iodinated albumin and myeloma proteins. J Clin Invest. 1958 Feb;37(2):272–284. doi: 10.1172/JCI103606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. HEINRICH R. A., VONDER HEIDE E. C., CLIMIE A. R. Cryofibrinogen: formation and inhibition in heparinized plasma. Am J Physiol. 1963 Mar;204:419–422. doi: 10.1152/ajplegacy.1963.204.3.419. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Hanauer L. B., Christian C. L. Studies of cryoproteins in systemic lupus erythematosus. J Clin Invest. 1967 Mar;46(3):400–408. doi: 10.1172/JCI105541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Jensen J. Anaphylatoxin in its relation to the complement system. Science. 1967 Mar 3;155(3766):1122–1123. doi: 10.1126/science.155.3766.1122. [DOI] [PubMed] [Google Scholar]
  17. LOSPALLUTO J., DORWARD B., MILLER W., Jr, ZIFF M. Cryoglobulinemia based on interaction between a gamma macroglobulin and 7S gamma globulin. Am J Med. 1962 Jan;32:142–147. doi: 10.1016/0002-9343(62)90191-2. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. MACKAY I. R., ERIKSEN N., MOTULSKY A. G., VOLWILER W. Cryo- and macroglobulinemia; electrophoretic, ultracentrifugal and clinical studies. Am J Med. 1956 Apr;20(4):564–587. doi: 10.1016/0002-9343(56)90139-5. [DOI] [PubMed] [Google Scholar]
  20. MARTIN R. G., AMES B. N. A method for determining the sedimentation behavior of enzymes: application to protein mixtures. J Biol Chem. 1961 May;236:1372–1379. [PubMed] [Google Scholar]
  21. Meltzer M., Franklin E. C. Cryoglobulinemia--a study of twenty-nine patients. I. IgG and IgM cryoglobulins and factors affecting cryoprecipitability. Am J Med. 1966 Jun;40(6):828–836. doi: 10.1016/0002-9343(66)90199-9. [DOI] [PubMed] [Google Scholar]
  22. PLOTZ C. M., SINGER J. M. The latex fixation test. I. Application to the serologic diagnosis of rheumatoid arthritis. Am J Med. 1956 Dec;21(6):888–892. [PubMed] [Google Scholar]
  23. ROSE N., PEETOOM F., RUDDY S., MICHELI A., GRABAR P. [Immunochemical study of hemolystates of human red cells. 1. Principle antigenic constituents]. Ann Inst Pasteur (Paris) 1960 Jan;98:70–89. [PubMed] [Google Scholar]
  24. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  25. SCHUR P. H., SANDSON J. Immunologic studies of the proteins of human synovial fluid. Arthritis Rheum. 1963 Apr;6:115–129. doi: 10.1002/art.1780060204. [DOI] [PubMed] [Google Scholar]
  26. Tan E. M., Kunkel H. G. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol. 1966 Mar;96(3):464–471. [PubMed] [Google Scholar]
  27. Tan E. M., Schur P. H., Carr R. I., Kunkel H. G. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1966 Nov;45(11):1732–1740. doi: 10.1172/JCI105479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. VAERMAN J. P., HEREMANS J. F., VAERMAN C. STUDIES OF THE IMMUNE GLOBULINS OF HUMAN SERUM. I. A METHOD FOR THE SIMULTANEOUS ISOLATION OF THE TREE IMMUNE GLOBULINS (GAMMA-SS, GAMMA-IM AND GAMMA-1A) FROM INDIVIDUAL SMALL SERUM SAMPLES. J Immunol. 1963 Jul;91:7–10. [PubMed] [Google Scholar]
  29. VOLPE R., BRUCE-ROBERTSON A., FLETCHER A. A., CHARLES W. B. Essential cryoglobulinaemia; review of the literature and report of a case treated with ACTH and cortisone. Am J Med. 1956 Apr;20(4):533–553. doi: 10.1016/0002-9343(56)90137-1. [DOI] [PubMed] [Google Scholar]
  30. Vaughan J. H., Barrnett E. V., Sobel M. V., Jacox R. F. Intracytoplasmic inclusions of immunoglobulins in rheumatoid arthritis and other diseases. Arthritis Rheum. 1968 Apr;11(2):125–134. doi: 10.1002/art.1780110202. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. ZVAIFLER N. J. A SPECULATION ON THE PATHOGENESIS OF JOINT INFLAMMATION IN RHEUMATOID ARTHRITIS. Arthritis Rheum. 1965 Apr;8:289–293. doi: 10.1002/art.1780080212. [DOI] [PubMed] [Google Scholar]
  33. da Silva W. D., Eisele J. W., Lepow I. H. Complement as a mediator of inflammation. 3. Purification of the activity with anaphylatoxin properties generated by interaction of the first four components of complement and its identification as a cleavage product of C'3. J Exp Med. 1967 Dec 1;126(6):1027–1048. doi: 10.1084/jem.126.6.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES