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. 1964 Mar 31;119(4):651–666. doi: 10.1084/jem.119.4.651

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

Melvin H Kaplan 1, Kathryn H Svec 1
PMCID: PMC2137853  PMID: 14151105

Abstract

Sera from patients with recent streptococcal infection or non-suppurative sequelae exhibit with variable frequency a precipitin reaction in agar gel with a partially purified streptococcal antigen which has been shown previously to be immunologically related to human heart tissue. This precipitin could be absorbed from sera with normal human heart tissue homogenates but not with homogenates of other organs. Demonstration of this cross-reaction by heart absorption was found dependent both upon the serologic properties of individual sera and the nature or state of purification of the streptococcal product employed as test antigen. Evidence was obtained of a close association of heart-related and non-heart-related antigenic determinants in partially purified preparations of the streptococcal antigen by both gel diffusion and immunoelectrophoresis. On immunoelectrophoretic analysis, cross-reactive antigen exhibited a more rapid mobility toward the anode than M protein. It was destroyed by digestion with trypsin, pepsin, and chymotrypsin. Based on specific absorption tests with a Type 5 and Type 19 strain, the antigen was localized to cell walls and to a lesser extent to cell membranes of these strains. Precipitating activity related to cross-reactive antibody was localized to the immunoglobulin zone in immunoelectrophoresis. Reactive sera showed diminution or loss of serological activity following heat inactivation at 56°C or after prolonged storage at 4°C. Sera containing cross-reactive precipitating antibody exhibited an immunofluorescent reaction with sarcolemma of cardiac myofibers, which was inhibited by streptococcal cross-reactive antigen. By this inhibition test, the immunofluorescent reaction related to cross-reactive antibody could be distinguished from that due to other heart-reactive factors. Antibody to streptococcal cross-reactive antigen defined by precipitation-absorption tests was observed in 24 per cent of patients with recent history of uncomplicated streptococcal infection and in the majority of patients with acute rheumatic fever, rheumatic heart disease, or acute glomerulonephritis. It was observed rarely in patients with non-streptococcal related disease. These data provide evidence that induction of cross-reactive autoantibody to heart in certain individuals is associated with streptococcal infection.

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Selected References

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

  1. CAYEUX P. [Immunological study of the precipitating antigen specific for Streptococcus pyogenes (Group A) type 24]. Ann Inst Pasteur (Paris) 1962 Jul;103:24–31. [PubMed] [Google Scholar]
  2. FREIMER E. H. Studies on L forms and protoplasts of group A streptococci. II. Chemical and immunological properties of the cell membrane. J Exp Med. 1963 Mar 1;117:377–399. doi: 10.1084/jem.117.3.377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. GERY I., DAVIES A. M. Organ specificity of the heart. I. Animal immunization with heterologous heart. J Immunol. 1961 Oct;87:351–356. [PubMed] [Google Scholar]
  4. KAPLAN M. H. IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS. I. PROPERTIES OF AN ANTIGEN IN CERTAIN STRAINS OF GROUP A STREPTOCOCCI EXHIBITING AN IMMUNOLOGIC CROSS-REACTION WITH HUMAN HEART TISSUE. J Immunol. 1963 Apr;90:595–606. [PubMed] [Google Scholar]
  5. KAPLAN M. H., MEYESERIAN M. An immunological cross-reaction between group-A streptococcal cells and human heart tissue. Lancet. 1962 Apr 7;1(7232):706–710. doi: 10.1016/s0140-6736(62)91653-7. [DOI] [PubMed] [Google Scholar]
  6. KAPLAN M. H., MEYESERIAN M. Immunologic studies of heart tissue. V. Antigens related to heart tissue revealed by cross-reaction of rabbit antisera to heterologous heart. J Immunol. 1962 Apr;88:450–461. [PubMed] [Google Scholar]
  7. KAPLAN M. H., MEYESERIAN M., KUSHNER I. Immunologic studies of heart tissue. IV. Serologic reactions with human heart tissue as revealed by immunofluorescent methods: isoimmune, Wassermann, and autoimmune reactions. J Exp Med. 1961 Jan 1;113:17–36. doi: 10.1084/jem.113.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KAPLAN M. H., SUCHY M. L. IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS. II. CROSS-REACTION OF ANTISERA TO MAMMALIAN HEART TISSUE WITH A CELL WALL CONSTITUENT OF CERTAIN STRAINS OF GROUP A STREPTOCOCCI. J Exp Med. 1964 Apr 1;119:643–650. doi: 10.1084/jem.119.4.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. KUNKEL H. G., TISELIUS A. Electrophoresis of proteins on filter paper. J Gen Physiol. 1951 Sep;35(1):89–118. doi: 10.1085/jgp.35.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LANCEFIELD R. C., PERLMANN G. E. Preparation and properties of type-specific M antigen isolated from a group A, type 1 hemolytic streptococcus. J Exp Med. 1952 Jul;96(1):71–82. doi: 10.1084/jem.96.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. LANCEFIELD R. C. Persistence of type-specific antibodies in man following infection with group A streptococci. J Exp Med. 1959 Aug 1;110(2):271–292. doi: 10.1084/jem.110.2.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. PRINGLE B. H., WILSON M. W. Cross-reactions in the Ouchterlony plant: analysis of native and halogenated bovine serum albumins. J Immunol. 1956 Nov;77(5):324–331. [PubMed] [Google Scholar]
  13. RICHTER M., ROSE B., SEHON A. H. The significance of the number of precipitin bands in agar gel medium for the determination of the complexity of antigens. Can J Biochem Physiol. 1958 Nov;36(11):1105–1113. [PubMed] [Google Scholar]
  14. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  15. SLADE H. D., VETTER J. K. Studies on Streptococcus pyogenes. I. Observations on the microscopical and biological aspects of the disintegration and solubilization of a type 6 strain by sonic oscillation. J Bacteriol. 1956 Feb;71(2):236–243. doi: 10.1128/jb.71.2.236-243.1956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. WILSON A. T., WILEY G. G. THE CELLULAR ANTIGENS OF GROUP A STREPTOCOCCI; IMMUNOELECTROPHORETIC STUDIES OF THE C, M, T, PGP, E4, F, AND E ANTIGENS OF SEROTYPE 17 STREPTOCOCCI. J Exp Med. 1963 Oct 1;118:527–556. doi: 10.1084/jem.118.4.527. [DOI] [PMC free article] [PubMed] [Google Scholar]

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