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. 1980 Jan;65(1):136–145. doi: 10.1172/JCI109643

Detection of immune complexes in acute rheumatic fever and their relationship to HLA-B5.

S Yoshinoya, R M Pope
PMCID: PMC371348  PMID: 6765956

Abstract

Employing five radioimmunoassays for immune complexes, the sera of 45 acute and 27 postacute follow-up sera from patients with acute rheumatic fever were examined. All patients experienced actue polyarthritis. Complexes were detected in 89% of acute-phase sera by one assay, 51% by two, 29% by three, and 7% by four. Immune complex values decreased significantly at followup, although some abnormalities persisted. There was no correlation between extra-articular manifestations and the occurrence of circulating immune complexes. Those positive for HLA-B5 demonstrated a significantly more pronounced immune response as measured by circulating immune complexes. The data indicate that circulating immune complexes occur frequently in adults with acute rheumatic fever. The relative frequency of immune complexes detected by multiple techniques in B5-positive, compared with B5-negative, patients suggests a genetic basis for the development of immune complexes in these patiemts.

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Selected References

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

  1. Barnert A. L., Terry E. E., Persellin R. H. Acute rheumatic fever in adults. JAMA. 1975 Jun 2;232(9):925–928. [PubMed] [Google Scholar]
  2. Casali P., Bossus A., Carpentier N. A., Lambert P. H. Solid-phase enzyme immunoassay or radioimmunoassay for the detection of immune complexes based on their recognition by conglutinin: conglutinin-binding test. A comparative study with 125I-labelled Clq binding and Raji-cell RIA tests. Clin Exp Immunol. 1977 Aug;29(2):342–354. [PMC free article] [PubMed] [Google Scholar]
  3. Caughey D. E., Douglas R., Wilson W., Hassall I. B. HL-A antigens in Europeans and Maoris with rheumatic fever and rheumatic heart disease. J Rheumatol. 1975 Sep;2(3):319–322. [PubMed] [Google Scholar]
  4. Cerottini J. C., Brunner K. T. Cell-mediated cytotoxicity, allograft rejection, and tumor immunity. Adv Immunol. 1974;18:67–132. doi: 10.1016/s0065-2776(08)60308-9. [DOI] [PubMed] [Google Scholar]
  5. Cochrane C. G., Hawkins D. Studies on circulating immune complexes. 3. Factors governing the ability of circulating complexes to localize in blood vessels. J Exp Med. 1968 Jan 1;127(1):137–154. doi: 10.1084/jem.127.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DEUTSCH H. F., MORTON J. I. Dissociation of human serum macroglobulins. Science. 1957 Mar 29;125(3248):600–601. doi: 10.1126/science.125.3248.600. [DOI] [PubMed] [Google Scholar]
  7. Dudding B. A., Ayoub E. M. Persistence of streptococcal group A antibody in patients with rheumatic valvular disease. J Exp Med. 1968 Nov 1;128(5):1081–1098. doi: 10.1084/jem.128.5.1081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Falk J. A., Fleischman J. L., Zabriskie J. B., Falk R. E. A study of HL-A antigen phenotype in rheumatic fever and rheumatic heart disease patients. Tissue Antigens. 1973;3(3):173–178. doi: 10.1111/j.1399-0039.1973.tb00991.x. [DOI] [PubMed] [Google Scholar]
  9. Fischel E. E., Pauli R. H., Lesh J. SEROLOGICAL STUDIES IN RHEUMATIC FEVER. II. SERUM COMPLEMENT IN THE RHEUMATIC STATE. J Clin Invest. 1949 Sep;28(5 Pt 2):1172–1181. doi: 10.1172/JCI102151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gabriel A., Jr, Agnello V. Detection of immune complexes. The use of radioimmunoassays with Clq and monoclonal rheumatoid factor. J Clin Invest. 1977 May;59(5):990–1001. doi: 10.1172/JCI108722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greenberg L. J., Gray E. D., Yunis E. J. Association of HL-A 5 and immune responsiveness in vitro to streptococcal antigens. J Exp Med. 1975 May 1;141(5):935–943. doi: 10.1084/jem.141.5.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HELMKAMP R. W., GOODLAND R. L., BALE W. F., SPAR I. L., MUTSCHLER L. E. High specific activity iodination of gamma-globulin with iodine-131 monochloride. Cancer Res. 1960 Nov;20:1495–1500. [PubMed] [Google Scholar]
  13. Hay F. C., Nineham L. J., Roitt I. M. Routine assay for the detection of immune complexes of known immunoglobulin class using solid phase C1q. Clin Exp Immunol. 1976 Jun;24(3):396–400. [PMC free article] [PubMed] [Google Scholar]
  14. Hellström K. E., Hellström I. Lymphocyte-mediated cytotoxicity and blocking serum activity to tumor antigens. Adv Immunol. 1974;18:209–277. doi: 10.1016/s0065-2776(08)60311-9. [DOI] [PubMed] [Google Scholar]
  15. Joysey V. C., Roger J. H., Ashworth F., Bullman W., Hazleman B. L., Lachmann S. M., Watson P. G. Parallel studies of HLA antigens in patients with rheumatic heart disease and scleritis: comparisons with three control populations. J Rheumatol Suppl. 1977;3:84–88. [PubMed] [Google Scholar]
  16. KAPLAN M. H., SVEC K. H. IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS. III. PRESENCE IN HUMAN SERA OF STREPTOCOCCAL ANTIBODY CROSS-REACTIVE WITH HEART TISSUE. ASSOCIATION WITH STREPTOCOCCAL INFECTION, RHEUMATIC FEVER, AND GLOMERULONEPHRITIS. J Exp Med. 1964 Apr 1;119:651–666. doi: 10.1084/jem.119.4.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kolb W. P., Kolb L. M., Podack E. R. C1q: isolation from human serum in high yield by affinity chromatography and development of a highly sensitive hemolytic assay. J Immunol. 1979 May;122(5):2103–2111. [PubMed] [Google Scholar]
  18. Krick E. H., De Heer D. H., Kaplan R. A., Arroyave C. M., Vaughan J. H. Metabolism of factor B of serum complement in rheumatoid arthritis. Clin Exp Immunol. 1978 Oct;34(1):1–9. [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Leirisalo M., Laitinen O., Tiilikainen A. HLA phenotypes in patients with rheumatic fever, rheumatic heart disease, and Yersinia arthritis. J Rheumatol Suppl. 1977;3:78–83. [PubMed] [Google Scholar]
  21. Lurhuma A. Z., Cambiaso C. L., Masson P. L., Heremans J. F. Detection of circulating antigen-antibody complexes by their inhibitory effect on the agglutination of IgG-coated particles by rheumatioid factor of Clq. Clin Exp Immunol. 1976 Aug;25(2):212–226. [PMC free article] [PubMed] [Google Scholar]
  22. Luthra H. S., McDuffie F. C., Hunder G. G., Samayoa E. A. Immune complexes in sera and synovial fluids of patients with rheumatoid arthritis. Radioimmunoassay with monocylonal rheumatoid factor. J Clin Invest. 1975 Aug;56(2):458–466. doi: 10.1172/JCI108112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mannik M., Arend M. P., Hall A. P., Gilliland B. C. Studies on antigen-antibody complexes. I. Elimination of soluble complexes from rabbit circulation. J Exp Med. 1971 Apr 1;133(4):713–739. doi: 10.1084/jem.133.4.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. McDevitt H. O., Benacerraf B. Genetic control of specific immune responses. Adv Immunol. 1969;11:31–74. doi: 10.1016/s0065-2776(08)60477-0. [DOI] [PubMed] [Google Scholar]
  25. Murray G. C., Montiel M. M., Persellin R. H. A study of HLA antigens in adults with acute rheumatic fever. Arthritis Rheum. 1978 Jul-Aug;21(6):652–656. doi: 10.1002/art.1780210607. [DOI] [PubMed] [Google Scholar]
  26. NISONOFF A., WISSLER F. C., LIPMAN L. N., WOERNLEY D. L. Separation of univalent fragments from the bivalent rabbit antibody molecule by reduction of disulfide bonds. Arch Biochem Biophys. 1960 Aug;89:230–244. doi: 10.1016/0003-9861(60)90049-7. [DOI] [PubMed] [Google Scholar]
  27. Nardella F. A., Mannik M. Nonimmunospecific protein-protein interactions of IgG: studies of the binding of IgG to IgG immunoadsorbents. J Immunol. 1978 Mar;120(3):739–744. [PubMed] [Google Scholar]
  28. Nicholas R., Sinclair S. C. Regulation of the immune response. I. Reduction in ability of specific antibody to inhibit long-lasting IgG immunological priming after removal of the Fc fragment. J Exp Med. 1969 Jun 1;129(6):1183–1201. doi: 10.1084/jem.129.6.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nydegger U. E., Zubler R. H., Gabay R., Joliat G., Karagevrekis C. H., Lambert P. H., Miescher P. A. Circulating complement breakdown products in patients with rheumatoid arthritis. Correlation between plasma C3d, circulating immune complexes, and clinical activity. J Clin Invest. 1977 May;59(5):862–868. doi: 10.1172/JCI108708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Read S. E., Fischetti V. A., Utermohlen V., Falk R. E., Zabriskie J. B. Cellular reactivity studies to streptococcal antigens. Migration inhibition studies in patients with streptococcal infections and rheumatic fever. J Clin Invest. 1974 Aug;54(2):439–450. doi: 10.1172/JCI107780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Read S. E., Reid H., Poon-King T., Fischetti V. A., Zabriskie J. B., Rapaport F. T. HLA and predisposition to the nonsuppurative sequelae of group A streptococcal infections. Transplant Proc. 1977 Mar;9(1):543–546. [PubMed] [Google Scholar]
  32. Rossen R. D., Zubler R. H., Day N. K., Reisberg M. A., Morgan A. C., Gutterman J. U., Hersh E. M. Detection of immune complex-like materials in cancer patients' sera: a comparative study of results obtained with the C1q deviation and C1q binding tests. J Lab Clin Med. 1978 Feb;91(2):191–204. [PubMed] [Google Scholar]
  33. SCHMIDT W. C., MOORE D. J. THE DETERMINATION OF ANTIBODY TO GROUP A STREPTOCOCCAL POLYSACCHARIDE IN HUMAN SERA BY HEMAGGLUTINATION. J Exp Med. 1965 May 1;121:793–806. doi: 10.1084/jem.121.5.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. STOLLERMAN G. H., LEWIS A. J., SCHULTZ I., TARANTA A. Relationship of immune response to group A streptococci to the course of acute, chronic and recurrent rheumatic fever. Am J Med. 1956 Feb;20(2):163–169. doi: 10.1016/0002-9343(56)90185-1. [DOI] [PubMed] [Google Scholar]
  35. Schubart A. F., Ewald R. W., Schroeder W. C., Rothschild H. J., Bhatavadekar D. N., Pullen P. K. Serum complement levels in rheumatoid arthritis. A longitudinal study of 43 cases with correlation of clinical and serological data including rheumatoid factor and thermolabile inhibitor of the F-II L.P. test. Ann Rheum Dis. 1965 Sep;24(5):439–450. doi: 10.1136/ard.24.5.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Svartman M., Potter E. V., Poon-King T., Earle D. P. Immunoglobulins and complement components in synovial fluid of patients with acute rheumatic fever. J Clin Invest. 1975 Jul;56(1):111–117. doi: 10.1172/JCI108059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Taranta A. Poststreptococcal diseases: pathogenetic aspects of rheumatic fever and acute poststreptococcal glomerulonephritis. Pathobiol Annu. 1978;8:333–357. [PubMed] [Google Scholar]
  38. 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]
  39. WANNAMAKER L. W., AYOUB E. M. Antibody titers in acute rheumatic fever. Circulation. 1960 Apr;21:598–614. doi: 10.1161/01.cir.21.4.598. [DOI] [PubMed] [Google Scholar]
  40. WILLIAMS R. C., Jr, LAW D. H., 4th Serum complement in connective tissue disorders. J Lab Clin Med. 1958 Aug;52(2):273–281. [PubMed] [Google Scholar]
  41. 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]
  42. Wilson C. B., Dixon F. J. Quantitation of acute and chronic serum sickness in the rabbit. J Exp Med. 1971 Sep 1;134(3 Pt 2):7s–8s. [PubMed] [Google Scholar]
  43. Yang L. C., Soprey P. R., Wittner M. K., Fox E. N. Streptococcal-induced cell-mediated-immune destruction of cardiac myofibers in vitro. J Exp Med. 1977 Aug 1;146(2):344–360. doi: 10.1084/jem.146.2.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Zabriskie J. B., Hsu K. C., Seegal B. C. Heart-reactive antibody associated with rheumatic fever: characterization and diagnostic significance. Clin Exp Immunol. 1970 Aug;7(2):147–159. [PMC free article] [PubMed] [Google Scholar]
  45. Zimmerman R. A., Auernheimer A. H., Taranta A. Precipitating antibody to group A streptococcal polysaccharide in humans. J Immunol. 1971 Sep;107(3):832–841. [PubMed] [Google Scholar]
  46. Zubler R. H., Lambert P. H. Detection of immune complexes in human diseases. Prog Allergy. 1978;24:1–48. [PubMed] [Google Scholar]
  47. 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]
  48. Zvaifler N. J. The immunopathology of joint inflammation in rheumatoid arthritis. Adv Immunol. 1973;16(0):265–336. doi: 10.1016/s0065-2776(08)60299-0. [DOI] [PubMed] [Google Scholar]
  49. van de Rijn I., Fillit H., Brandeis W. E., Reid H., Poon-King T., McCarthy M., Day N. K., Zabriskie J. B. Serial studies on circulating immune complexes in post-streptococcal sequelae. Clin Exp Immunol. 1978 Dec;34(3):318–325. [PMC free article] [PubMed] [Google Scholar]
  50. van de Rijn I., Zabriskie J. B., McCarty M. Group A streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen. J Exp Med. 1977 Aug 1;146(2):579–599. doi: 10.1084/jem.146.2.579. [DOI] [PMC free article] [PubMed] [Google Scholar]

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