Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1967 Apr;46(4):539–548. doi: 10.1172/JCI105555

Evidence for In Vivo Breakdown of β1C-Globulin in Hypocomplementemic Glomerulonephritis *

Clark D West 1,2,, Sara Winter 1,2, Judith Forristal 1,2, Janice M McConville 1,2, Neil C Davis 1,2
PMCID: PMC442037  PMID: 4164258

Abstract

Evidence has been obtained for the presence in vivo of alpha2D-globulin, a breakdown product of serum β1C-globulin, in patients with acute and persistent hypocomplementemic glomerulonephritis. The protein has been identified by immunoelectrophoretic analysis, and the amounts present have been determined by direct measurement of specific antigenic determinants present on alpha2D. β1A-Globulin, another breakdown product of β1C-globulin, may also be present in vivo in severely hypocomplementemic patients, but its levels are much lower than those of alpha2D-globulin.

Alpha2D-globulin has been identified by immunoelectrophoretic analysis of fresh EDTA plasma from patients with hypocomplementemic nephritis as an arc in the alpha2 region that shows a reaction of identity with the arc representing alpha2D-globulin produced by aged normal serum. β1A-Globulin was not seen in these patterns.

Measurement of specific antigenic determinants has been carried out in both fresh EDTA plasma and aged serum. In the fresh plasma, the concentration of D antigen, found on both β1C- and alpha2D-globulins, has been related to that of B antigen, found only on β1C and taken as a measure of the concentration of this protein. In the hypocomplementemic patients, the concentration of D antigen, in comparison to that of B, was greater than in the normal subjects. Similarly, in aged serum, the level of alpha2D was greater than would be expected from the amount of β1C that had been broken down in vitro, measured by the concentration of β1A.

Calculations indicated that the in vivo alpha2D level in severely hypocomplementemic patients ranged from 7.5 to 18% of that which would be found in a pool of aged normal serum in which β1C is completely broken down. The levels tended to be lower in less severely hypocomplementemic patients, and none could be detected in normal plasma.

Only small quantities of A and D antigens are detectable in the urine of patients with hypocomplementemic nephritis. The rate of excretion is about equal to that of the normal subject.

The study indicates that the low serum levels of β1C-globulin that may be present over long periods in patients with persistent hypocomplementemic glomerulonephritis can be ascribed, in part, to in vivo breakdown of this protein as a result of reaction with immune complexes. The contribution of β1C deposition on immune complexes and of diminished synthesis to the depressed serum levels cannot be assessed by the present study.

Full text

PDF
542

Images in this article

Selected References

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

  1. Alper C. A., Levin A. S., Rosen F. S. Beta-1C-globulin: metabolism in glomerulonephritis. Science. 1966 Jul 8;153(3732):180–182. doi: 10.1126/science.153.3732.180. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. MORSE J. H., MULLER-EBERHARD H. J., KUNKEL H. G. Anti-nuclear factors and serum complement in systemic lupus erythematosus. Bull N Y Acad Med. 1962 Oct;38:641–651. [PMC free article] [PubMed] [Google Scholar]
  4. Müllerèberhard H. J., Dalmasso A. P., Calcott M. A. The reaction mechanism of beta-1C-globulin (C'3) in immune hemolysis. J Exp Med. 1966 Jan 1;123(1):33–54. doi: 10.1084/jem.123.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  6. WEST C. D., HINRICHS V., HINKLE N. H. Quantitative determination of the serum globulins beta-2A and beta-2M by immunoelectrophoretic analysis. J Lab Clin Med. 1961 Jul;58:137–148. [PubMed] [Google Scholar]
  7. WEST C. D., NORTHWAY J. D., DAVIS N. C. SERUM LEVELS OF BETA-1C GLOBULIN, A COMPLEMENT COMPONENT, IN THE NEPHRITIDES, LIPOID NEPHROSIS, AND OTHER CONDITIONS. J Clin Invest. 1964 Aug;43:1507–1517. doi: 10.1172/JCI105027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES