Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Sep;89(3):479–484. doi: 10.1111/j.1365-2249.1992.tb06984.x

Significance of C3 nephritic factor (C3NeF) in non-hypocomplementaemic serum with membranoproliferative glomerulonephritis (MPGN).

H Ohi 1, S Watanabe 1, T Fujita 1, T Yasugi 1
PMCID: PMC1554488  PMID: 1516262

Abstract

C3NeF is an autoantibody of C3 convertase (C3bBb) and is often detected in the serum of hypocomplementaemic MPGN patients. Serum samples from 104 non-hypocomplementaemic MPGN patients (C3NeF) were studied. C3NeF, which cannot activate the alternative pathway, was found in the sera of 6 patients. We examined the C3NeF in purified IgG from five of the non-hypocomplementaemic serum samples (non-hypo C3NeF) and four hypocomplementaemic serum samples (hypocomplementaemic C3NeF) to determine why C3NeF does not induce C3 splitting and hypocomplementaemia. Purified IgG from non-hypo C3NeF stabilized EAC4b3bBb cells in a manner similar to IgG from hypocomplementaemic C3NeF in EDTA gelatin veronal buffer. However, the non-hypo C3NeF IgG did not stabilize C3 convertase (EAC4b3bBb cells) in the presence of control proteins (factors H and I), whereas the hypocomplementaemic C3NeF IgG did. The C3NeF in the hypocomplementaemic serum displayed two characteristics: (i) inhibition of intrinsic decay of Ce convertase (C3bBb); and (ii) inhibition of extrinsic decay by factors H and I. Although the C3NeF in the non-hypocomplementaemic sera did inhibit the intrinsic decay in a manner similar to the hypocomplementaemic C3NeF IgG, it did not inhibit the extrinsic decay. Due to the different characteristics of hypocomplementaemic C3NeF and non-hypo C3NeF in the serum samples, the non-hypo C3NeF did not activate C3. Therefore, we conclude that C3NeF exhibits a heterogeneity which is very important in relation to the pathogenesis of MPGN.

Full text

PDF
482

Selected References

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

  1. Brandslund I., Siersted H. C., Svehag S. E., Teisner B. Double-decker rocket immunoelectrophoresis for direct quantitation of complement C3 split products with C3d specificities in plasma. J Immunol Methods. 1981;44(1):63–71. doi: 10.1016/0022-1759(81)90107-1. [DOI] [PubMed] [Google Scholar]
  2. Daha M. R., Fearon D. T., Austen K. F. C3 nephritic factor (C3NeF): stabilization of fluid phase and cell-bound alternative pathway convertase. J Immunol. 1976 Jan;116(1):1–7. [PubMed] [Google Scholar]
  3. Daha M. R., Van Es L. A. Stabilization of homologous and heterologous cell-bound amplification convertases, C3bBb, by C3 nephritic factor. Immunology. 1981 May;43(1):33–38. [PMC free article] [PubMed] [Google Scholar]
  4. Gigli I., Sorvillo J., Halbwachs-Mecarelli L. Regulation and deregulation of the fluid-phase classical pathway C3 convertase. J Immunol. 1985 Jul;135(1):440–444. [PubMed] [Google Scholar]
  5. Halbwachs L., Leveillé M., Lesavre P., Wattel S., Leibowitch J. Nephritic factor of the classical pathway of complement: immunoglobulin G autoantibody directed against the classical pathway C3 convetase enzyme. J Clin Invest. 1980 Jun;65(6):1249–1256. doi: 10.1172/JCI109787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Nagaki K., Iida K., Inai S. A new method for the preparation of EAC14 cell with human or guinea-pig serum. J Immunol Methods. 1974 Aug;5(3):307–317. doi: 10.1016/0022-1759(74)90117-3. [DOI] [PubMed] [Google Scholar]
  7. Ohi H., Tanuma Y., Hatano M. Is membranoproliferative glomerulonephritis an autoimmune disease? Nephron. 1990;54(2):192–192. doi: 10.1159/000185849. [DOI] [PubMed] [Google Scholar]
  8. Ohi H., Watanabe S., Fujita T., Seki M., Hatano M. Detection of C3bBb-stabilizing activity (C3 nephritic factor) in the serum from patients with membranoproliferative glomerulonephritis. J Immunol Methods. 1990 Jul 20;131(1):71–76. doi: 10.1016/0022-1759(90)90234-m. [DOI] [PubMed] [Google Scholar]
  9. Scott D. M., Amos N., Sissons J. G., Lachmann P. J., Peters D. K. The immunogloblin nature of nephritic factor (NeF). Clin Exp Immunol. 1978 Apr;32(1):12–24. [PMC free article] [PubMed] [Google Scholar]
  10. Sissons J. G., West R. J., Fallows J., Williams D. G., Boucher B. J., Amos N., Peters D. K. The complement abnormalities of lipodystrophy. N Engl J Med. 1976 Feb 26;294(9):461–465. doi: 10.1056/NEJM197602262940902. [DOI] [PubMed] [Google Scholar]
  11. Spitzer R. E., Stitzel A. E., Tsokos G. C. Evidence that production of autoantibody to the alternative pathway C3 convertase is a normal physiologic event. J Pediatr. 1990 May;116(5):S103–S108. doi: 10.1016/s0022-3476(05)82711-8. [DOI] [PubMed] [Google Scholar]
  12. Spitzer R. E., Stitzel A. E., Tsokos G. C. Human anti-idiotypic antibody responses to autoantibody against the alternative pathway C3 convertase. Clin Immunol Immunopathol. 1990 Oct;57(1):19–31. doi: 10.1016/0090-1229(90)90019-m. [DOI] [PubMed] [Google Scholar]
  13. Spitzer R. E., Stitzel A. E., Tsokos G. C. Production of IgG and IgM autoantibody to the alternative pathway C3 convertase in normal individuals and patients with membranoproliferative glomerulonephritis. Clin Immunol Immunopathol. 1990 Oct;57(1):10–18. doi: 10.1016/0090-1229(90)90018-l. [DOI] [PubMed] [Google Scholar]
  14. Spitzer R. E., Vallota E. H., Forristal J., Sudora E., Stitzel A., Davis N. C., West C. D. Serum C'3 lytic system in patients with glomerulonephritis. Science. 1969 Apr 25;164(3878):436–437. doi: 10.1126/science.164.3878.436. [DOI] [PubMed] [Google Scholar]
  15. Strife C. F., Prada A. L., Clardy C. W., Jackson E., Forristal J. Autoantibody to complement neoantigens in membranoproliferative glomerulonephritis. J Pediatr. 1990 May;116(5):S98–102. doi: 10.1016/s0022-3476(05)82710-6. [DOI] [PubMed] [Google Scholar]
  16. Tanuma Y., Ohi H., Hatano M. Two types of C3 nephritic factor: properdin-dependent C3NeF and properdin-independent C3NeF. Clin Immunol Immunopathol. 1990 Aug;56(2):226–238. doi: 10.1016/0090-1229(90)90144-f. [DOI] [PubMed] [Google Scholar]
  17. Tanuma Y., Ohi H., Watanabe S., Seki M., Hatano M. C3 nephritic factor and C4 nephritic factor in the serum of two patients with hypocomplementaemic membranoproliferative glomerulonephritis. Clin Exp Immunol. 1989 Apr;76(1):82–85. [PMC free article] [PubMed] [Google Scholar]
  18. Weiler J. M., Daha M. R., Austen K. F., Fearon D. T. Control of the amplification convertase of complement by the plasma protein beta1H. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3268–3272. doi: 10.1073/pnas.73.9.3268. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES