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. 1978 Nov;34(2):179–187.

Activation of the alternate complement pathway in Staph. aureus infective endocarditis and its relationship to thrombocytopenia, coagulation abnormalities, and acute glomerulonephritis.

D T O'Connor, M H Weisman, J Fierer
PMCID: PMC1537484  PMID: 737901

Abstract

Twenty-four patients with infective endocarditis (IE) are described, fourteen with Staph. aureus and ten with other organisms. Despite the acute nature of the infection, ten of the fourteen with Staph. aureus IE were hypocomplementaemic; six of these ten had normal levels of C4 associated with low C3 levels, suggesting activation of the alternate complement pathway. Factor B (C3PA) was also low in three of these six cases. In the ten patients with non-Staph. IE, three had hypocomplementaemia with low levels of C4, C3, and Factor B, probably due to C1 (classical pathway) activation with feedback activation of the alternate pathway. In addition, thrombocytopenia was noted in nine of the twenty-four patients and was associated with hypocomplementaemia; the degree of renal insufficiency noted in these patients also correlated with hypocomplementaemia. In Staph. aureus IE thrombocytopenia and hypocomplementaemia, occurring early in the course of the disease, may be due to a non-immune interaction of Staph. cell wall products (Protein A) with immunoglobulin, complement components, and thrombocytes.

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Selected References

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

  1. Bayer A. S., Theofilopoulos A. N., Eisenberg R., Dixon F. J., Guze L. B. Circulating immune complexes in infective endocarditis. N Engl J Med. 1976 Dec 30;295(27):1500–1505. doi: 10.1056/NEJM197612302952703. [DOI] [PubMed] [Google Scholar]
  2. Cherubin C. E., Neu H. C. Infective endocarditis at the Presbyterian Hospital in New York City from 1938-1967. Am J Med. 1971 Jul;51(1):83–96. doi: 10.1016/0002-9343(71)90326-3. [DOI] [PubMed] [Google Scholar]
  3. Churchill M. A., Jr, Geraci J. E., Hunder G. G. Musculoskeletal manifestations of bacterial endocarditis. Ann Intern Med. 1977 Dec;87(6):754–759. doi: 10.7326/0003-4819-87-6-754. [DOI] [PubMed] [Google Scholar]
  4. Crowder J. G., White A. Teichoic acid antibodies in staphylococcal and nonstaphylococcal endocarditis. Ann Intern Med. 1972 Jul;77(1):87–90. doi: 10.7326/0003-4819-77-1-87. [DOI] [PubMed] [Google Scholar]
  5. Davis J. A., Weisman M. H., Dail D. H. Vascular disease in infective endocarditis. Report of immune-mediated events in skin and brain. Arch Intern Med. 1978 Mar;138(3):480–483. doi: 10.1001/archinte.138.3.480. [DOI] [PubMed] [Google Scholar]
  6. Eisenberg R. A., Theofilopoulos A. N., Dixon F. J. Use of bovine conglutinin for the assay of immune complexes. J Immunol. 1977 Apr;118(4):1428–1434. [PubMed] [Google Scholar]
  7. Forristal J., Iitaka K., Vallota E. H., West C. D. Correlations between serum factor B and C3b inactivator levels in normal subjects and in patients with infections, nephrosis and hypocomplementaemic glomerulonephritis. Clin Exp Immunol. 1977 Apr;28(1):61–71. [PMC free article] [PubMed] [Google Scholar]
  8. Forsgren A. Significance of protein a production by staphylococci. Infect Immun. 1970 Nov;2(5):672–673. doi: 10.1128/iai.2.5.672-673.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Forsgren A., Sjöquist J. "Protein A" from S. aureus. I. Pseudo-immune reaction with human gamma-globulin. J Immunol. 1966 Dec;97(6):822–827. [PubMed] [Google Scholar]
  10. Gutman R. A., Striker G. E., Gilliland B. C., Cutler R. E. The immune complex glomerulonephritis of bacterial endocarditis. Medicine (Baltimore) 1972 Jan;51(1):1–25. doi: 10.1097/00005792-197201000-00001. [DOI] [PubMed] [Google Scholar]
  11. Hunder G. G., McDuffie F. C., Hepper N. G. Pleural fluid complement in systemic lupus erythematosus and rheumatoid arthritis. Ann Intern Med. 1972 Mar;76(3):357–363. doi: 10.7326/0003-4819-76-3-357. [DOI] [PubMed] [Google Scholar]
  12. KENT J. F., FIFE E. H., Jr Precise standardization of reagents for complement fixation. Am J Trop Med Hyg. 1963 Jan;12:103–116. doi: 10.4269/ajtmh.1963.12.103. [DOI] [PubMed] [Google Scholar]
  13. Kronvall G., Gewurz H. Activation and inhibition of IgG mediated complement fixation by staphylococcal protein A. Clin Exp Immunol. 1970 Aug;7(2):211–220. [PMC free article] [PubMed] [Google Scholar]
  14. Laxdal T., Messner R. P., Williams R. C., Jr, Quie P. G. Opsonic, agglutinating, and complement-fixing antibodies in patients with subacute bacterial endocarditis. J Lab Clin Med. 1968 Apr;71(4):638–653. [PubMed] [Google Scholar]
  15. Lewis E. J., Carpenter C. B., Schur P. H. Serum complement component levels in human glomerulonephritis. Ann Intern Med. 1971 Oct;75(4):555–560. doi: 10.7326/0003-4819-75-4-555. [DOI] [PubMed] [Google Scholar]
  16. Messner R. P., Laxdal T., Quie P. G., Williams R. C., Jr Rheumatoid factors in subacute bacterial endocarditis--bacterium, duration of disease or genetic predisposition? Ann Intern Med. 1968 Apr;68(4):746–756. doi: 10.7326/0003-4819-68-4-746. [DOI] [PubMed] [Google Scholar]
  17. POWELL D. E. Non-suppurative lesions in staphylococcal septicaemia. J Pathol Bacteriol. 1961 Jul;82:141–149. doi: 10.1002/path.1700820117. [DOI] [PubMed] [Google Scholar]
  18. Pelletier L. L., Jr, Petersdorf R. G. Infective endocarditis: a review of 125 cases from the University of Washington Hospitals, 1963-72. Medicine (Baltimore) 1977 Jul;56(4):287–313. [PubMed] [Google Scholar]
  19. Pertschuk L. P., Woda B. A., Vuletin J. C., Brigati D. J., Soriano C. B., Nicastri A. D. Glomerulonephritis due to Staphylococcus aureus antigen. Am J Clin Pathol. 1976 Mar;65(3):301–307. doi: 10.1093/ajcp/65.3.301. [DOI] [PubMed] [Google Scholar]
  20. RABINOVICH S., EVANS J., SMITH I. M., JANUARY L. E. A LONG-TERM VIEW OF BACTERIAL ENDOCARDITIS. 337 CASES 1924 TO 1963. Ann Intern Med. 1965 Aug;63:185–198. doi: 10.7326/0003-4819-63-2-185. [DOI] [PubMed] [Google Scholar]
  21. Rahal J. J., Jr, MacMahon H. E., Weinstein L. Thrombocytopenia and symmetrical peripheral gangrene associated with staphylococcal and streptococcal bacteremia. Ann Intern Med. 1968 Jul;69(1):35–43. doi: 10.7326/0003-4819-69-1-35. [DOI] [PubMed] [Google Scholar]
  22. Rogers D. E., Melly M. A. Speculations on the immunology of staphylococcal infections. Ann N Y Acad Sci. 1965 Jul 23;128(1):274–284. doi: 10.1111/j.1749-6632.1965.tb11644.x. [DOI] [PubMed] [Google Scholar]
  23. Schutte M., DiCamelli R., Murphy P., Sadove M., Gewurz H. C3 proactivator (C3PA) as an acute phase reactant. Clin Exp Immunol. 1974 Oct;18(2):251–256. [PMC free article] [PubMed] [Google Scholar]
  24. Sjöquist J., Stålenheim G. Protein A from Staphylococcus aureus. IX. Complement-fixing activity of protein A-IgG complexes. J Immunol. 1969 Sep;103(3):467–473. [PubMed] [Google Scholar]
  25. Stickler G. B., Shin M. H., Burke E. C., Holley K. E., Miller R. H., Segar W. E. Diffuse glomerulonephritis associated with infected ventriculoatrial shunt. N Engl J Med. 1968 Nov 14;279(20):1077–1082. doi: 10.1056/NEJM196811142792003. [DOI] [PubMed] [Google Scholar]
  26. Stålenheim G., Götze O., Cooper N. R., Sjöquist J., Müller-Eberhard H. J. Consumption of human complement components by complexes of IgG with protein A of Staphylococcus aureus. Immunochemistry. 1973 Aug;10(8):501–507. doi: 10.1016/0019-2791(73)90221-8. [DOI] [PubMed] [Google Scholar]
  27. Tu W. H., Shearn M. A., Lee J. C. Acute diffuse glomerulonephritis in acute staphylococcal endocarditis. Ann Intern Med. 1969 Aug;71(2):335–341. doi: 10.7326/0003-4819-71-2-335. [DOI] [PubMed] [Google Scholar]
  28. WILLIAMS R. C., Jr, KUNKEL H. G. Rheumatoid factor, complement, and conglutinin aberrations in patients with subacute bacterial endocarditis. J Clin Invest. 1962 Mar;41:666–675. doi: 10.1172/JCI104523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yoshida K., Ekstedt R. D. Relation of mucoid growth of Staphylococcus aureus to clumping factor reaction, morphology in serum-soft agar, and virulence. J Bacteriol. 1968 Oct;96(4):902–908. doi: 10.1128/jb.96.4.902-908.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zimmerman T. S., Fierer J., Rothberger H. Blood coagulation and the inflammatory response. Semin Hematol. 1977 Oct;14(4):391–408. [PubMed] [Google Scholar]

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