Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1976 Aug;84(2):283–298.

Membranoproliferative glomerulonephritis. Localization of early components of complement in glomerular deposits.

B K Davis, T Cavallo
PMCID: PMC2032448  PMID: 133617

Abstract

A body of evidence suggests that in membranoproliferative glomerulonephritis (MPGN), complement is activated by the alternate pathway. Therefore, deposition of early components of complement should not be expected in glomeruli. The renal tissues of 16 patients--13 with classic MPGN and 3 with dense deposit disease, a variant of MPGN--were studied by light and electron microscopy and by means of elution and immunofluorescence for the localization of complement (C1q, C4, and C3), immunoglobulins (1gG, IgM, and 1gA), and other serum proteins. Variable amounts of C3, C4 and/or C1q, and IgM were detected in the glomeruli of all patients, whereas IgG and IgA were present, respectively, in 15 of 16 and 6 of 16 patients. Deposits were localized in mesangium and in peripheral capillary loops in a typical lobular distribution. The specificity of each antiserum was verified by immunodiffusion, immunoelectrophoresis, and blocking experiments utilizing unlabeled antibody. Glomerular-bound IgG was eluted with acid citrate buffer, suggesting that IgG might be complexed with antigen(s) in glomerular deposits. By light microscopy, lesions ranged from focal proliferation and lobulation to more severe involvement with typical splitting of glomerular basement membranes, sclerosis, and less frequently, crescent formation. Ultrastructurally, all patients with classic MPGN exhibited mesangial and subendothelial deposits, and in 5 of these patients, subepithelial deposits were demonstrated. With the exception of ultrastructural lesions, patients with the dense deposit variant lacked distinguishable features when compared with those with classic MPGN. The significance of these findings is discussed in relation to a) activation of complement and the possible role of an immune complex mechanism and b) the variability of the morphologic expression.

Full text

PDF
284

Images in this article

Selected References

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

  1. Burkholder P. M., Marchand A., Krueger R. P. Mixed membranous and proliferative glomerulonephritis. A correlative light, immunofluorescence, and electron microscopic study. Lab Invest. 1970 Nov;23(5):459–479. [PubMed] [Google Scholar]
  2. COONS A. H., KAPLAN M. H. Localization of antigen in tissue cells; improvements in a method for the detection of antigen by means of fluorescent antibody. J Exp Med. 1950 Jan 1;91(1):1–13. doi: 10.1084/jem.91.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cameron J. S., Glasgow E. F., Ogg C. S., White R. H. Membranoproliferative glomerulonephritis and persistent hypocomplementaemia. Br Med J. 1970 Oct 3;4(5726):7–14. doi: 10.1136/bmj.4.5726.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Galle P., Mahieu P. Electron dense alteration of kidney basement membranes. A renal lesion specific of a systemic disease. Am J Med. 1975 Jun;58(6):749–764. doi: 10.1016/0002-9343(75)90631-2. [DOI] [PubMed] [Google Scholar]
  6. Gewurz H., Pickering R. J., Mergenhagen S. E., Good R. A. The complement profile in acute glomerulonephritis systemic lupus erythematosus and hypocomplementemic chronic glomerulonephritis. Contrasts and experimental correlations. Int Arch Allergy Appl Immunol. 1968;34(6):556–570. doi: 10.1159/000230149. [DOI] [PubMed] [Google Scholar]
  7. Grishman E., Porush J. C., Rosen S. M., Churg J. Lupus nephritis with organized deposits in the kidneys. Lab Invest. 1967 May;16(5):717–725. [PubMed] [Google Scholar]
  8. Habib R., Gubler M. C., Loirat C., Mäiz H. B., Levy M. Dense deposit disease: a variant of membranoproliferative glomerulonephritis. Kidney Int. 1975 Apr;7(4):204–215. doi: 10.1038/ki.1975.32. [DOI] [PubMed] [Google Scholar]
  9. Habib R., Loirat C., Gubler M., Levy M. Morphology and serum complement levels in membranoproliferative glomerulonephritis. Adv Nephrol Necker Hosp. 1974;4:109–136. [PubMed] [Google Scholar]
  10. Jenis E. H., Sandler P., Hill G. S., Knieser M. R., Jensen G. E., Roskes S. D. Glomerulonephritis with basement membrane dense deposits. Arch Pathol. 1974 Feb;97(2):84–91. [PubMed] [Google Scholar]
  11. Lagrue G., Sobel A., Bariety J., Hirbec G., Druet P. Les glomérulonphrites pariéto prolifératives hypocomplémentaires. 28 observations. Nouv Presse Med. 1973 Sep 29;2(34):2253–2259. [PubMed] [Google Scholar]
  12. 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]
  13. Lewis E. J., Cavallo T., Harrington J. T., Cotran R. S. An immunopathologic study of rapidly progressive glomerulonephritis in the adult. Hum Pathol. 1971 Jun;2(2):185–208. doi: 10.1016/s0046-8177(71)80034-5. [DOI] [PubMed] [Google Scholar]
  14. Mandalenakis N., Mendoza N., Pirani C. L., Pollak V. E. Lobular glomerulonephritis and membranoproliferative glomerulonephritis: a clinical and pathologic study based on renal biopsies. Medicine (Baltimore) 1971 Jul;50(4):319–355. [PubMed] [Google Scholar]
  15. McLean R. H., Townsend K., Michael A. F. The effect of anticomplementary substances on properdin in normal and C2-deficient sera. Clin Exp Immunol. 1975 Mar;19(3):435–444. [PMC free article] [PubMed] [Google Scholar]
  16. Michael A. F., Herdman R. C., Fish A. J., Pickering R. J., Vernier R. L. Chronic membranoproliferative glomerulonephritis with hypocomplementemia. Transplant Proc. 1969 Dec;1(4):925–932. [PubMed] [Google Scholar]
  17. Michael A. F., McLean R. H. Evidence for activation of the alternate pathway in glomerulonephritis. Adv Nephrol Necker Hosp. 1974;4:49–66. [PubMed] [Google Scholar]
  18. Michael A. F., Westberg N. G., Fish A. J., Vernier R. L. Studies on chronic membranoproliferative glomerulonephritis with hypocomplementemia. J Exp Med. 1971 Sep 1;134(3 Pt 2):208s–227s. [PubMed] [Google Scholar]
  19. Perrin L. H., Lambert P. H., Miescher P. A. Properdin levels in systemic lupus erythematosus and membranoproleferative glomerulonephritis. Clin Exp Immunol. 1974 Apr;16(4):575–581. [PMC free article] [PubMed] [Google Scholar]
  20. Peters D. K., Williams D. G. Complement and mesangiocapillary glomerulonephritis: the role of complement deficiency in glomerulonephritis. Adv Nephrol Necker Hosp. 1974;4:67–78. [PubMed] [Google Scholar]
  21. Pickering R. J., Herdman R. C., Michael A. F., Vernier R. L., Gewurz H., Fish A. J., Good R. A. Chronic glomerulonephritis associated with low serum complement activity (chronic hypocomplementemic glomerulonephritis). Medicine (Baltimore) 1970 May;49(3):207–226. doi: 10.1097/00005792-197005000-00002. [DOI] [PubMed] [Google Scholar]
  22. Ploem J. S. A study of filters and light sources in immunofluorescence microscopy. Ann N Y Acad Sci. 1971 Jun 21;177:414–429. doi: 10.1111/j.1749-6632.1971.tb35070.x. [DOI] [PubMed] [Google Scholar]
  23. Verroust P. J., Wilson C. B., Cooper N. R., Edgington T. S., Dixon F. J. Glomerular complement components in human glomerulonephritis. J Clin Invest. 1974 Jan;53(1):77–84. doi: 10.1172/JCI107562. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. West C. D. Membranoproliferative hypocomplementemic glomerulonephritis. Nephron. 1973;11(2):134–146. doi: 10.1159/000180226. [DOI] [PubMed] [Google Scholar]
  25. West C. D. Membranoproliferative hypocomplementemic glomerulonephritis. Nephron. 1973;11(2):134–146. doi: 10.1159/000180226. [DOI] [PubMed] [Google Scholar]
  26. West C. D., Ruley E. J., Forristal J., Davis N. C. Mechanisms of hypocomplementemia in glomerulonephritis. Kidney Int. 1973 Feb;3(2):116–125. doi: 10.1038/ki.1973.18. [DOI] [PubMed] [Google Scholar]
  27. Westberg N. G., Naff G. B., Boyer J. T., Michael A. F. Glomerular deposition of properdin in acute and chronic glomerulonephritis with hypocomplementemia. J Clin Invest. 1971 Mar;50(3):642–649. doi: 10.1172/JCI106534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Williams D. G., Peters D. K., Fallows J., Petrie A., Kourilsky O., Morel-Maroger L., Cameron J. S. Studies of serum complement in the hypocomplementaemic nephritides. Clin Exp Immunol. 1974 Nov;18(3):391–405. [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES