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Lupus nephritis: a nucleosome waste disposal defect?
Jo H M Berden1, Cecile Grootscholten, W C Dieker Jürgen
1Nephrology Research Laboratory, Nijmegen Center for Molecular Life Sciences Division of Nephrology, University Medical Center, Nijmegen, The Netherlands. J.Berden@nier.umcn.nl
Journal of Nephrology
|January 8, 2003
Summary
Systemic lupus erythematosus (SLE) involves autoantibodies against nucleosomes, the main autoantigen. Released nucleosomes during apoptosis contribute to lupus nephritis by binding to glomerular structures.
Area of Science:
- Immunology
- Rheumatology
- Cell Biology
Background:
- Systemic lupus erythematosus (SLE) is characterized by autoantibodies.
- Nucleosomes are now recognized as the primary autoantigen in SLE.
- Nucleosome-specific T cells drive the production of anti-dsDNA and anti-histone antibodies.
Purpose of the Study:
- To elucidate the role of nucleosomes as a major autoantigen in systemic lupus erythematosus (SLE).
- To investigate the contribution of nucleosomes to the pathogenesis of lupus nephritis.
Main Methods:
- Identification of nucleosome-specific T cells in SLE patients.
- Analysis of autoantibody profiles in SLE patients and lupus mice.
- Examination of nucleosomes and autoantibodies in kidney biopsies from lupus nephritis patients.
Main Results:
- Nucleosome-specific autoantibodies are prevalent in most SLE patients and lupus models.
- Nucleosomes are released during apoptosis when clearance mechanisms are overwhelmed or impaired.
- Modified nucleosomes become more immunogenic.
- Nucleosomes, anti-nucleosome antibodies, and complexes are found in glomerular deposits in lupus nephritis.
- Nucleosomes bind to glomerular basement membranes via cationic histone components.
Conclusions:
- Nucleosomes are central autoantigens in SLE, driving autoantibody formation.
- The release and modification of nucleosomes during apoptosis contribute to SLE pathogenesis.
- Nucleosomes play a significant role in the development of lupus nephritis through interactions with the glomerular basement membrane.