Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1988 Sep;73(3):479–483.

Lack of complement activation by human IgA immune complexes.

H Imai 1, A Chen 1, R J Wyatt 1, A Rifai 1
PMCID: PMC1541773  PMID: 3061690

Abstract

Complement activation may play an important role in renal injury associated with glomerular deposition of IgA immune complexes. The ability of naturally occurring human IgA immune complexes (IgA-IC) and covalently cross-linked human IgA oligomers (X-IgA) to activate complement were examined in vitro and in vivo. Large-sized IgA-IC were isolated from a patient's serum by affinity purification (Jacalin-Sepharose) and gel chromatography. Stable X-IgA were prepared by chemical cross-linking with a heterobifunctional reagent, N-succinimdyl 3-(2-pyridyl-dithio) propionate (SPDP). Treatment of fresh normal human serum with large amounts of either IgA-IC or X-IgA failed to activate C3. The C3 consumption was measured immunochemically by the decrease of the B antigen on the native C3 and by the generation of iC3b. Addition of these complexes to serum did not result in cleavage of factor B. Administration of human IgA-IC or X-IgA to mice, killed after 6 h, resulted in glomerular deposition of IgA. Despite the presence of intense glomerular IgA deposits no C3 was detected. Collectively, these findings suggest that neither soluble nor renal localized human IgA complexes activate complement.

Full text

PDF
479

Selected References

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

  1. Boackle R. J., Pruitt K. M., Mestecky J. The interactions of human complement with interfacially aggregated preparations of human secretory IgA. Immunochemistry. 1974 Sep;11(9):543–548. doi: 10.1016/0019-2791(74)90245-6. [DOI] [PubMed] [Google Scholar]
  2. Clarkson A. R., Woodroffe A. J., Aarons I., Hiki Y., Hale G. IgA nephropathy. Annu Rev Med. 1987;38:157–168. doi: 10.1146/annurev.me.38.020187.001105. [DOI] [PubMed] [Google Scholar]
  3. Colten H. R., Bienenstock J. Lack of C3 activation through classical or alternate pathways by human secretory IgA anti blood group A antibody. Adv Exp Med Biol. 1974;45(0):305–308. doi: 10.1007/978-1-4613-4550-3_36. [DOI] [PubMed] [Google Scholar]
  4. Ey P. L., Prowse S. J., Jenkin C. R. Complement-fixing IgG1 constitutes a new subclass of mouse IgG. Nature. 1979 Oct 11;281(5731):492–493. doi: 10.1038/281492a0. [DOI] [PubMed] [Google Scholar]
  5. Glassock R. J., Kurokawa K., Yoshida M., Sakai O., Okada M., Shigematsu H., Ohno J., Sakai H. IgA nephropathy in Japan. Am J Nephrol. 1985;5(2):127–137. doi: 10.1159/000166919. [DOI] [PubMed] [Google Scholar]
  6. Götze O., Müller-Eberhard H. J. The C3-activator system: an alternate pathway of complement activation. J Exp Med. 1971 Sep 1;134(3 Pt 2):90s–108s. [PubMed] [Google Scholar]
  7. Hiemstra P. S., Gorter A., Stuurman M. E., Van Es L. A., Daha M. R. Activation of the alternative pathway of complement by human serum IgA. Eur J Immunol. 1987 Mar;17(3):321–326. doi: 10.1002/eji.1830170304. [DOI] [PubMed] [Google Scholar]
  8. Imai H., Chen A., Wyatt R. J., Rifai A. Composition of IgA immune complexes precipitated with polyethylene glycol. A model for isolation and analysis of immune complexes. J Immunol Methods. 1987 Nov 5;103(2):239–245. doi: 10.1016/0022-1759(87)90295-x. [DOI] [PubMed] [Google Scholar]
  9. Julian B. A., Wyatt R. J., McMorrow R. G., Galla J. H. Serum complement proteins in IgA nephropathy. Clin Nephrol. 1983 Nov;20(5):251–258. [PubMed] [Google Scholar]
  10. Klaus G. G., Pepys M. B., Kitajima K., Askonas B. A. Activation of mouse complement by different classes of mouse antibody. Immunology. 1979 Dec;38(4):687–695. [PMC free article] [PubMed] [Google Scholar]
  11. Levinsky R. J., Barratt T. M. IgA immune complexes in Henoch-Schönlein purpura. Lancet. 1979 Nov 24;2(8152):1100–1103. doi: 10.1016/s0140-6736(79)92505-4. [DOI] [PubMed] [Google Scholar]
  12. Magilavy D. B., Rifai A., Plotz P. H. An abnormality of immune complex kinetics in murine lupus. J Immunol. 1981 Feb;126(2):770–774. [PubMed] [Google Scholar]
  13. Marder H. K., Coleman T. H., Forristal J., Beischel L., West C. D. An inherited defect in the C3 convertase, C3b,Bb, associated with glomerulonephritis. Kidney Int. 1983 May;23(5):749–758. doi: 10.1038/ki.1983.89. [DOI] [PubMed] [Google Scholar]
  14. Rifai A., Chen A., Imai H. Complement activation in experimental IgA nephropathy: an antigen-mediated process. Kidney Int. 1987 Dec;32(6):838–844. doi: 10.1038/ki.1987.284. [DOI] [PubMed] [Google Scholar]
  15. Rifai A., Mannik M. Clearance kinetics and fate of mouse IgA immune complexes prepared with monomeric or dimeric IgA. J Immunol. 1983 Apr;130(4):1826–1832. [PubMed] [Google Scholar]
  16. Roque-Barreira M. C., Campos-Neto A. Jacalin: an IgA-binding lectin. J Immunol. 1985 Mar;134(3):1740–1743. [PubMed] [Google Scholar]
  17. Shirai T., Tomino Y., Sato M., Yoshiki T., Itoh T. IgA nephropathy: clinicopathology and immunopathology. Contrib Nephrol. 1978;9:88–100. doi: 10.1159/000401436. [DOI] [PubMed] [Google Scholar]
  18. Tamerius J. D., Pangburn M. K., Müller-Eberhard H. J. Detection of a neoantigen on human C3bi and C3d by monoclonal antibody. J Immunol. 1985 Sep;135(3):2015–2019. [PubMed] [Google Scholar]
  19. Valentijn R. M., Kauffmann R. H., de la Rivière G. B., Daha M. R., Van ES L. A. Presence of circulating macromolecular IgA in patients with hematuria due to primary IgA nephropathy. Am J Med. 1983 Mar;74(3):375–381. doi: 10.1016/0002-9343(83)90954-3. [DOI] [PubMed] [Google Scholar]
  20. Waldo F. B., Forristal J., Beischel L., West C. D. A circulating inhibitor of fluid-phase amplification. C3 convertase formation in systemic lupus erythematosus. J Clin Invest. 1985 Jun;75(6):1786–1795. doi: 10.1172/JCI111891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. West C., Davis N. C., Forristal J., Herbst J., Spitzer R. Antigenic determinants of human beta-1c and beta-1g-globulins. J Immunol. 1966 Apr;96(4):650–658. [PubMed] [Google Scholar]
  22. Wyatt R. J., Kanayama Y., Julian B. A., Negoro N., Sugimoto S., Hudson E. C., Curd J. G. Complement activation in IgA nephropathy. Kidney Int. 1987 Apr;31(4):1019–1023. doi: 10.1038/ki.1987.101. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES