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Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo.

Publication ,  Journal Article
Vlahakos, D; Foster, MH; Ucci, AA; Barrett, KJ; Datta, SK; Madaio, MP
Published in: J Am Soc Nephrol
February 1992

The production of relatively high quantities of autoantibodies (autoAb) that react with DNA and other intranuclear antigens is characteristic of individuals with systemic lupus erythematosus and other autoimmune diseases. However, the capacity of these Ab to penetrate cells and induce functional perturbations in vivo is not well appreciated. To address this issue, monoclonal (m) anti-DNA Ab (mAb), derived from MRL-lpr/lpr and (NZB x SWR)F1 mice, were administered to normal mice, and the animals were examined for morphologic and functional abnormalities. A subset of five mAb produced intranuclear immunoglobulin deposits in multiple organs. Intranuclear immunoglobulin deposits were also observed after cross-linking the tissue before direct immunofluorescence and after i.v. injection of F(ab')2 fragments of one anti-DNA Ab. This phenomenon was reproducible and was only associated with this subset of autoAb. Furthermore, intranuclear deposits of anti-DNA Ab within glomeruli were associated with morphologic and functional abnormalities including: hypercellularity, epithelial foot process fusion, new fiber bundle formation within the mesangium suggestive of new collagen synthesis, and proteinuria. These results indicate that a subset of autoAb may penetrate cells in vivo to influence normal cellular and nuclear function and to contribute to functional and pathologic abnormalities in individuals with systemic lupus.

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Published In

J Am Soc Nephrol

DOI

ISSN

1046-6673

Publication Date

February 1992

Volume

2

Issue

8

Start / End Page

1345 / 1354

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Proteinuria
  • Microscopy, Fluorescence
  • Mice, Inbred Strains
  • Mice
  • Lupus Erythematosus, Systemic
  • Kidney Glomerulus
  • Immunoglobulin Fab Fragments
  • Hybridomas
  • Cell Nucleus
 

Citation

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Vlahakos, D., Foster, M. H., Ucci, A. A., Barrett, K. J., Datta, S. K., & Madaio, M. P. (1992). Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo. J Am Soc Nephrol, 2(8), 1345–1354. https://doi.org/10.1681/ASN.V281345
Vlahakos, D., M. H. Foster, A. A. Ucci, K. J. Barrett, S. K. Datta, and M. P. Madaio. “Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo.J Am Soc Nephrol 2, no. 8 (February 1992): 1345–54. https://doi.org/10.1681/ASN.V281345.
Vlahakos D, Foster MH, Ucci AA, Barrett KJ, Datta SK, Madaio MP. Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo. J Am Soc Nephrol. 1992 Feb;2(8):1345–54.
Vlahakos, D., et al. “Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo.J Am Soc Nephrol, vol. 2, no. 8, Feb. 1992, pp. 1345–54. Pubmed, doi:10.1681/ASN.V281345.
Vlahakos D, Foster MH, Ucci AA, Barrett KJ, Datta SK, Madaio MP. Murine monoclonal anti-DNA antibodies penetrate cells, bind to nuclei, and induce glomerular proliferation and proteinuria in vivo. J Am Soc Nephrol. 1992 Feb;2(8):1345–1354.

Published In

J Am Soc Nephrol

DOI

ISSN

1046-6673

Publication Date

February 1992

Volume

2

Issue

8

Start / End Page

1345 / 1354

Location

United States

Related Subject Headings

  • Urology & Nephrology
  • Proteinuria
  • Microscopy, Fluorescence
  • Mice, Inbred Strains
  • Mice
  • Lupus Erythematosus, Systemic
  • Kidney Glomerulus
  • Immunoglobulin Fab Fragments
  • Hybridomas
  • Cell Nucleus