The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 12 January 2004 doi:10.1084/jem.20031519
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 2, 255-264
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 266K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Waters, S. T.
Right arrow Articles by Fu, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Waters, S. T.
Right arrow Articles by Fu, S. M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
Breaking Tolerance to Double Stranded DNA, Nucleosome, and Other Nuclear Antigens Is Not Required for the Pathogenesis of Lupus Glomerulonephritis

Samuel T. Waters1,2,3, Marcia McDuffie1,2,3, Harini Bagavant1,2, Umesh S. Deshmukh1,2, Felicia Gaskin1,4,5, Chao Jiang1,2,3, Kenneth S.K. Tung1,3,6, and Shu Man Fu1,2,3

1 The University of Virginia Specialized Center of Research on Systemic Lupus Erythematosus, University of Virginia School of Medicine, Charlottesville, VA 22908
2 Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908
3 Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908
4 Department of Psychiatric Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908
5 Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA 22908
6 Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA 22908

Address correspondence to Shu Man Fu, Division of Rheumatology and Immunology, Department of Internal Medicine, University of Virginia School of Medicine, Box 800412, Charlottesville, VA 22908. Phone: (434) 924-9627; Fax: (434) 924-9578; email: sf2e{at}virginia.edu

In lupus-prone NZM2328 mice, a locus Cgnz1 on chromosome 1 was linked to chronic glomerulonephritis, severe proteinuria, and early mortality in females. A locus Adnz1 on chromosome 4 was linked to antinuclear antibody (ANA) and anti–double stranded DNA (dsDNA) antibody (Ab) production. In this investigation, two congenic strains, NZM2328.C57L/Jc1 (NZM.C57Lc1) and NZM2328.C57L/Jc4 (NZM.C57Lc4), were generated by replacing the respective genetic intervals containing either Cgnz1 or Adnz1 with those from C57L/J, a nonlupus-prone strain. The NZM.C57Lc1 females had markedly reduced incidence of chronic glomerulonephritis and severe proteinuria. NZM.C57Lc4 females had chronic glomerulonephritis and severe proteinuria without circulating ANA, anti-dsDNA, and antinucleosome Ab. These data confirm the linkage analysis. Unexpectedly, NZM.C57Lc1 females had little anti-dsDNA and related Ab, suggesting the presence of a second locus Adnz2 on chromosome 1. The diseased NZM.C57Lc4 kidneys had immune complexes by immunofluorescence and electron microscopy. The eluates from these kidneys did not contain ANA, anti-dsDNA, and antinucleosome Ab, indicative of the presence of non–anti-dsDNA nephritogenic Ab. Thus, breaking tolerance to dsDNA and chromatin is not required for the pathogenesis of lupus nephritis. These results reaffirm that anti-dsDNA and related Ab production and chronic glomerulonephritis are under independent genetic control. These findings have significant implications in the pathogenesis of systemic lupus erythematosus.

Key Words: lupus autoantibodies • glomerulonephritis • NZM2328 • genetics

This work was presented in abstract form at the ACR 64th Annual Scientific Meeting at Philadelphia, PA in November, 2000 (Arthritis Rheum. 43:S361).

Abbreviations used in this paper: ANA, antinuclear Ab; dsDNA, double stranded DNA; EM, electron microscopic; NZM.C57Lc1, NZM2328.C57L/Jc1; NZM.C57Lc4, NZM2328.C57L/Jc4; SLE, systemic lupus erythematosus.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS