Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1977 Sep;74(9):3980–3983. doi: 10.1073/pnas.74.9.3980

Heterogeneity of nephritic factor and its identification as an immunoglobulin.

A E Davis 3rd, J B Ziegler, E W Gelfand, F S Rosen, C A Alper
PMCID: PMC431810  PMID: 269447

Abstract

Complement C3 nephritic factor (NeF) produces alternative pathway-meciated C3 cleavage by binding to and stabilizing the alternative pathway C3 convertase, C3bBb. Some studies have suggested that NeF is an immunoglobulin, while others conclude that it is a distinct serum protein. The heterogeneity of NeF was evaluated by electrophoresis and isoelectric focusing of NeF-containing serum followed by hemolytic demonstration of NeF activity in agar gel. With each method, diffuse cathodal zones or multiple bands of hemolysis developed, which revealed remarkable variations in patterns from patient to patient. NeF activity was absorbed by and eluted from insolubilized antibody to Fc and Fab fragments of IgG. Immunoabsorption of six NeF-containing sera with insolubilized anti-kappa and anti-lambda light chain antisera revealed that NeF had kappa antigenic determinants in three, lambda antigenic determinants in one, and both kappa and lambda antigenic determinants in two. These data indicate that NeF is an oligoclonal immunoglobulin. Because NeF binds to the alternative pathway C3 convertase, C3bBb, we suggest that it is an antibody to a conformational antigen of the C3-factor B complex, and thereby stabilizes this complex.

Full text

PDF
3980

Images in this article

3981Image
on p.3981
3981Image
on p.3981

Selected References

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

  1. Alper C. A., Bloch K. J., Rosen F. S. Increased susceptibility to infection in a patient with type II essential hypercatabolism of C3. N Engl J Med. 1973 Mar 22;288(12):601–606. doi: 10.1056/NEJM197303222881204. [DOI] [PubMed] [Google Scholar]
  2. Alper C. A., Colten H. R., Rosen F. S., Rabson A. R., Macnab G. M., Gear J. S. Homozygous deficiency of C3 in a patient with repeated infections. Lancet. 1972 Dec 2;2(7788):1179–1181. doi: 10.1016/s0140-6736(72)92598-6. [DOI] [PubMed] [Google Scholar]
  3. Amos N., Sissons J. G., Girard J. F., Lachmann P. J., Peters D. K. The cofactors required by C3 nephritic factor to generate a C3 convertase in vitro. Clin Exp Immunol. 1976 Jun;24(3):474–482. [PMC free article] [PubMed] [Google Scholar]
  4. Arroyave C. M., Wilson M. R., Tan E. M. Serum factors activating the alternative complement pathway in autoimmune disease: description of two different factors from patients with systemic lupus erythematosus. J Immunol. 1976 Mar;116(3):821–826. [PubMed] [Google Scholar]
  5. Avrameas S., Ternynck T. Biologically active water-insoluble protein polymers. I. Their use for isolation of antigens and antibodies. J Biol Chem. 1967 Apr 10;242(7):1651–1659. [PubMed] [Google Scholar]
  6. Awdeh Z. L., Williamson A. R., Askonas B. A. Isoelectric focusing in polyacrylamide gel and its application to immunoglobulins. Nature. 1968 Jul 6;219(5149):66–67. doi: 10.1038/219066a0. [DOI] [PubMed] [Google Scholar]
  7. Berthoux F. C., Carpenter C. B., Traeger J., Merrill J. P. The C3 nephritic factor (C3NeF) and the heat labile complement inactivator (HLCI) in chronic hypocomplementemic mesangioproliferative glomerulonephritis. Adv Nephrol Necker Hosp. 1974;4:91–108. [PubMed] [Google Scholar]
  8. Boenisch T., Alper C. A. Isolation and properties of a glycine-rich beta-glycoprotein of human serum. Biochim Biophys Acta. 1970 Dec 22;221(3):529–535. doi: 10.1016/0005-2795(70)90224-2. [DOI] [PubMed] [Google Scholar]
  9. Border W. A., Wilson C. B., Götze O. Nephritic factor: Description of a new quantitative assay and findings in glomerulonephritis. Kidney Int. 1976 Oct;10(4):311–318. doi: 10.1038/ki.1976.114. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Davis A. E., 3rd, Arnaout M. A., Alper C. A., Rosen F. S. Transfer of C3 nephritic factor from mother to fetus. Is C3 nephritic factor IgG? N Engl J Med. 1977 Jul 21;297(3):144–145. doi: 10.1056/NEJM197707212970306. [DOI] [PubMed] [Google Scholar]
  12. GOTOFF S. P., FELLERS F. X., VAWTER G. F., JANEWAY C. A., ROSEN F. S. THE BETA-1C GLOBULIN IN CHILDHOOD NEPHROTIC SYNDROME: LABORATORY DIAGNOSIS OF PROGRESSIVE GLOMERULONEPHRITIS. N Engl J Med. 1965 Sep 2;273:524–529. doi: 10.1056/NEJM196509022731004. [DOI] [PubMed] [Google Scholar]
  13. Ipp M. M., Minta J. O., Gelfand E. W. Disorders of the complement system in lipodystrophy. Clin Immunol Immunopathol. 1977 Mar;7(2):281–287. doi: 10.1016/0090-1229(77)90055-1. [DOI] [PubMed] [Google Scholar]
  14. LAURELL C. B. ANTIGEN-ANTIBODY CROSSED ELECTROPHORESIS. Anal Biochem. 1965 Feb;10:358–361. doi: 10.1016/0003-2697(65)90278-2. [DOI] [PubMed] [Google Scholar]
  15. Martin A., Lachmann P. J., Halbwachs L., Hobart M. J. Haemolytic diffusion plate assays for factors B and D of the alternative pathway of complement activation. Immunochemistry. 1976 Apr;13(4):317–324. doi: 10.1016/0019-2791(76)90341-4. [DOI] [PubMed] [Google Scholar]
  16. NILSSON U. R., MUELLER-EBERHARD H. J. ISOLATION OF BETA IF-GLOBULIN FROM HUMAN SERUM AND ITS CHARACTERIZATION AS THE FIFTH COMPONENT OF COMPLEMENT. J Exp Med. 1965 Aug 1;122:277–298. doi: 10.1084/jem.122.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ruley E. J., Forristal J., Davis N. C., Andres C., West C. D. Hypocomplementemia of membranoproliferative nephritis. Dependence of the nephritic factor reaction on properdin factor B. J Clin Invest. 1973 Apr;52(4):896–904. doi: 10.1172/JCI107254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Schreiber R. D., Götze O., Müller-Eberhard H. J. Alternative pathway of complement: demonstration and characterization of initiating factor and its properdin-independent function. J Exp Med. 1976 Oct 1;144(4):1062–1075. doi: 10.1084/jem.144.4.1062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schreiber R. D., Götze O., Müller-Eberhard H. J. Nephritic factor: its structure and function and its relationship to initiating factor of the alternative pathway. Scand J Immunol. 1976;5(6-7):705–713. doi: 10.1111/j.1365-3083.1976.tb03020.x. [DOI] [PubMed] [Google Scholar]
  20. Schreiber R. D., Medicus R. G., Gïtze O., Müller-Eberhard H. J. Properdin- and nephritic factor-dependent C3 convertases: requirement of native C3 for enzyme formation and the function of bound C3b as properdin receptor. J Exp Med. 1975 Sep 1;142(3):760–772. doi: 10.1084/jem.142.3.760. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Thompson R. A. C3 inactivating factor in the serum of a patient with chronic hypocomplementaemic proliferative glomerulo-nephritis. Immunology. 1972 Jan;22(1):147–158. [PMC free article] [PubMed] [Google Scholar]
  24. Vallota E. H., Götze O., Spiegelberg H. L., Forristal J., West C. D., Müller-Eberhard H. J. A serum factor in chronic hypocomplementemic hephritis distinct from immunoglobulins and activating the alternate pathway of complement. J Exp Med. 1974 May 1;139(5):1249–1261. doi: 10.1084/jem.139.5.1249. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES