Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1981 Dec 1;154(6):1779–1794. doi: 10.1084/jem.154.6.1779

Renal localization of the membrane attack complex in systemic lupus erythematosus nephritis

PMCID: PMC2186538  PMID: 7033435

Abstract

The membrane attack complex (MAC) of the complement system was localized in both glomeruli and peritubular regions of 22 kidneys manifesting systemic lupus erythematosus (SLE) nephritis. A similar distribution was observed for immune complex markers (IgG, Clq, and C3) and MAC in glomeruli, although the deposits of MAC were more discrete and showed lesser immunofluorescence staining intensity compared with immunoglobulins and complement components. In contrast, peritubular immune complexes were present in only 7 out of 22 kidneys, involved comparatively small clusters of tubules, exhibited weaker immunofluorescence staining than MAC, and failed to correlate with interstitial foci of inflammation. Granular or irregular, linear aggregates of the MAC were observed at the periphery of larger groups of tubules contiguous to areas of interstitial inflammation. Comparable amounts of IgG, Clq, C3, and MAC were present in blood vessel walls in areas of fibrinoid necrosis. These data suggest that the MAC is a direct mediator of tissue injury occurring in renal glomeruli, tubules, and blood vessels. The discordance between immune complexes and MAC localized in the peritubular region, but not in glomeruli or blood vessels, raises the possibility that both immune complexes and nonimmune agents, such as bacterial antigens, may activate the classical or alternative complement pathways and thereby play a role in the pathogenesis of tubulointerstitial lesions of SLE nephritis.

Full Text

The Full Text of this article is available as a PDF (3.1 MB).

Selected References

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

  1. Abrass C. K., Nies K. M., Louie J. S., Border W. A., Glassock R. J. Correlation and predictive accuracy of circulating immune complexes with disease activity in patients with systemic lupus erythematosus. Arthritis Rheum. 1980 Mar;23(3):273–282. doi: 10.1002/art.1780230302. [DOI] [PubMed] [Google Scholar]
  2. Adu D., Dobson J., Williams D. G. DNA-anti-DNA circulating complexes in the nephritis of systemic lupus erythematosus. Clin Exp Immunol. 1981 Mar;43(3):605–614. [PMC free article] [PubMed] [Google Scholar]
  3. Agnello V., Koffler D., Kunkel H. G. Immune complex systems in the nephritis of systemic lupus erythematosus. Kidney Int. 1973 Feb;3(2):90–99. doi: 10.1038/ki.1973.15. [DOI] [PubMed] [Google Scholar]
  4. Andres G. A., Accinni L., Beiser S. M., Christian C. L., Cinotti G. A., Erlanger B. F., Hsu K. C., Seegal B. C. Localization of fluorescein-labeled antinucleoside antibodies in glomeruli of patients with active systemic lupus erythematosus nephritis. J Clin Invest. 1970 Nov;49(11):2106–2118. doi: 10.1172/JCI106428. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Andres G. A., McCluskey R. T. Tubular and interstitial renal disease due to immunologic mechanisms. Kidney Int. 1975 Apr;7(4):271–289. doi: 10.1038/ki.1975.38. [DOI] [PubMed] [Google Scholar]
  6. Biesecker G., Müller-Eberhard H. J. The ninth component of human complement: purification and physicochemical characterization. J Immunol. 1980 Mar;124(3):1291–1296. [PubMed] [Google Scholar]
  7. Biesecker G., Podack E. R., Halverson C. A., Müller-Eberhard H. J. C5b-9 dimer: isolation from complement lysed cells and ultrastructural identification with complement-dependent membrane lesions. J Exp Med. 1979 Feb 1;149(2):448–458. doi: 10.1084/jem.149.2.448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bruneau C. D., Edmonds J. P., Hughes G. R., Aarden L. Detection and characterization of DNA-anti-DNA complexes in a patient with systemic lupus erythematosus. Clin Exp Immunol. 1977 Jun;28(3):433–436. [PMC free article] [PubMed] [Google Scholar]
  9. Cano P. O., Jerry L. M., Sladowski J. P., Osterland C. K. Circulating immune complexes in systemic lupus erythematosus. Clin Exp Immunol. 1977 Aug;29(2):197–204. [PMC free article] [PubMed] [Google Scholar]
  10. Caulfield J. P. Alterations in the distribution of Alcian blue-staining fibrillar anionic sites in the glomerular basement membrane in aminonucleoside nephrosis. Lab Invest. 1979 Apr;40(4):503–511. [PubMed] [Google Scholar]
  11. Curd J. G., Sundsmo J. S., Kolb W. P., Bluestein H. G., Müller-Eberhard H. J. Neoantigen of the membrane attack complex of human complement: Occurrence on peripheral blood leukocytes from patients with systemic lupus erythematosus. Arthritis Rheum. 1978 Mar;21(2):177–182. doi: 10.1002/art.1780210201. [DOI] [PubMed] [Google Scholar]
  12. Davis P., Cumming R. H., Verrier-Jones J. Relationship between anti-DNA antibodies complement consumption and circulating immune complexes in systemic lupus erythematosus. Clin Exp Immunol. 1977 May;28(2):226–232. [PMC free article] [PubMed] [Google Scholar]
  13. Fearon D. T., Austen K. F. Current concepts in immunology: the alternative pathway of complement--a system for host resistance to microbial infection. N Engl J Med. 1980 Jul 31;303(5):259–263. doi: 10.1056/NEJM198007313030505. [DOI] [PubMed] [Google Scholar]
  14. Gilliam J. N., Cheatum D. E., Hurd E. R., Stastny P., Ziff M. Immunoglobulin in clinically uninvolved skin in systemic lupus erythematosus: association with renal disease. J Clin Invest. 1974 May;53(5):1434–1440. doi: 10.1172/JCI107691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hu V. W., Esser A. F., Podack E. R., Wisnieski B. J. The membrane attack mechanism of complement: photolabeling reveals insertion of terminal proteins into target membrane. J Immunol. 1981 Jul;127(1):380–386. [PubMed] [Google Scholar]
  16. KNIKER W. T., COCHRANE C. G. PATHOGENIC FACTORS IN VASULAR LESIONS OF EXPERIMENTAL SERUM SICKNESS. J Exp Med. 1965 Jul 1;122:83–98. doi: 10.1084/jem.122.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koffler D., Agnello V., Carr R. I., Kunkel H. G. Variable patterns of immunoglobulin and complement deposition in the kidneys of patients with systemic lupus erythematosus. Am J Pathol. 1969 Sep;56(3):305–316. [PMC free article] [PubMed] [Google Scholar]
  18. Koffler D., Agnello V., Kimkel H. G. Polynucleotide immune complexes in serum and glomeruli of patients with systemic lupus erythematosus. Am J Pathol. 1974 Jan;74(1):109–124. [PMC free article] [PubMed] [Google Scholar]
  19. Koffler D., Carr R., Agnello V., Thoburn R., Kunkel H. G. Antibodies to polynucleotides in human sera: antigenic specificity and relation to disease. J Exp Med. 1971 Jul 1;134(1):294–312. doi: 10.1084/jem.134.1.294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Koffler D., Schur P. H., Kunkel H. G. Immunological studies concerning the nephritis of systemic lupus erythematosus. J Exp Med. 1967 Oct 1;126(4):607–624. doi: 10.1084/jem.126.4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kolb W. P., Müller-Eberhard H. J. Neoantigens of the membrane attack complex of human complement. Proc Natl Acad Sci U S A. 1975 May;72(5):1687–1689. doi: 10.1073/pnas.72.5.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Levinsky R. J., Cameron J. S., Soothill J. F. Serum immune complexes and disease activity in lupus nephritis. Lancet. 1977 Mar 12;1(8011):564–567. doi: 10.1016/s0140-6736(77)91998-5. [DOI] [PubMed] [Google Scholar]
  23. Miller T. E., Lahita R. G., Zarro V. J., MacWilliam J., Koffler D. Clinical significance of anti-double-stranded DNA antibodies detected by a solid phase enzyme immunoassay. Arthritis Rheum. 1981 Apr;24(4):602–610. doi: 10.1002/art.1780240406. [DOI] [PubMed] [Google Scholar]
  24. Müller-Eberhard H. J. Complement. Annu Rev Biochem. 1975;44:697–724. doi: 10.1146/annurev.bi.44.070175.003405. [DOI] [PubMed] [Google Scholar]
  25. Patrick C. C., Virella G., McManus J. F., Faulk W. P., Hughson H. D., Fudenberg H. H. Induction of extraglomerular renal damage in experimental chronic serum sickness. I. Histologic and immunofluorescence findings. Lab Invest. 1979 May;40(5):603–614. [PubMed] [Google Scholar]
  26. Pinckard R. N., O'Rourke R. A., Crawford M. H., Grover F. S., McManus L. M., Ghidoni J. J., Storrs S. B., Olson M. S. Complement localization and mediation of ischemic injury in baboon myocardium. J Clin Invest. 1980 Nov;66(5):1050–1056. doi: 10.1172/JCI109933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Podack E. R., Müller-Eberhard H. J. SC5b-9 complex of complement: formation of the dimeric membrane attack complex by removal of S-protein. J Immunol. 1980 Apr;124(4):1779–1783. [PubMed] [Google Scholar]
  28. Provost T. T., Andres G., Maddison P. J., Reichlin M. Lupus band test in untreated SLE patients: correlation of immunoglobulin deposition in the skin of the extensor forearm with clinical renal disease and serological abnormalities. J Invest Dermatol. 1980 Jun;74(6):407–412. doi: 10.1111/1523-1747.ep12544532. [DOI] [PubMed] [Google Scholar]
  29. Raptis L., Menard H. A. Quantitation and characterization of plasma DNA in normals and patients with systemic lupus erythematosus. J Clin Invest. 1980 Dec;66(6):1391–1399. doi: 10.1172/JCI109992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sahashi K., Engel A. G., Lambert E. H., Howard F. M., Jr Ultrastructural localization of the terminal and lytic ninth complement component (C9) at the motor end-plate in myasthenia gravis. J Neuropathol Exp Neurol. 1980 Mar;39(2):160–172. doi: 10.1097/00005072-198003000-00005. [DOI] [PubMed] [Google Scholar]
  31. Schur P. H., Sandson J. Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med. 1968 Mar 7;278(10):533–538. doi: 10.1056/NEJM196803072781004. [DOI] [PubMed] [Google Scholar]
  32. Sugisaki T., Klassen J., Milgrom F., Andres G. A., McCluskey R. T. Immunopathologic study of an autoimmune tubular and interstitial renal disease in brown Norway rats. Lab Invest. 1973 Jun;28(6):658–671. [PubMed] [Google Scholar]
  33. Tan E. M., Schur P. H., Carr R. I., Kunkel H. G. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1966 Nov;45(11):1732–1740. doi: 10.1172/JCI105479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tron F., Ganeval D., Droz D. Immunologically-mediated acute renal failure of nonglomerular origin in the course of systemic lupus erythematosus [SLE]. Report of two cases. Am J Med. 1979 Sep;67(3):529–532. doi: 10.1016/0002-9343(79)90806-4. [DOI] [PubMed] [Google Scholar]
  35. Unanue E. R., Dixon F. J., Feldman J. D. Experimental allergic glomerulonephritis induced in the rabbit with homologous renal antigens. J Exp Med. 1967 Jan 1;125(1):163–176. doi: 10.1084/jem.125.1.163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Winfield J. B., Koffler D., Kunkel H. G. Specific concentration of polynucleotide immune complexes in the cryoprecipitates of patients with systemic lupus erythematosus. J Clin Invest. 1975 Sep;56(3):563–570. doi: 10.1172/JCI108125. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES