Lupus nephritis: a nucleosome waste disposal defect?
Formation of anti-nuclear autoantibodies is a cardinal characteristic of systemic lupus erythematosus (SLE). In recent years the nucleosome has been identified as the major autoantigen, since nucleosome specific T cells have been identified, which also drive the formation of anti-dsDNA and anti-histone antibodies. Nucleosome specific autoantibodies are present in a large majority of SLE patients and lupus mice. Nucleosomes are formed during apoptosis by organized cleavage of chromatin. These nucleosomes together with other lupus autoantigens cluster in apoptotic bodies at the surface of apoptotic cells. Systemic release of these autoantigens is normally prevented by swift removal of apoptotic cels. However, if the rate of apoptosis overflows the removal capacity and/or the cleaning machinery is reduced, nucleosomes are released. Furthermore, during apoptosis autoantigens can be modified, which makes them more immunogenic. Nucleosomes also play a pivotal role in the evolution of tissue lesions, especially glomerulonephritis. In lupus nephritis nucleosomes, anti-nucleosome autoantibodies and nucleosome/Ig complexes have been identified in the glomerular immune deposits. Via their cationic histone part nucleosomes can bind to heparan sulfate, a strong anionic constituent of the glomerular basement membrane.
Berden
Jo H M
JH
Nephrology Research Laboratory, Nijmegen Center for Molecular Life Sciences Division of Nephrology, University Medical Center, Nijmegen, The Netherlands. J.Berden@nier.umcn.nl
Grootscholten
Cecile
C
Jürgen
W C Dieker
WC
van der Vlag
Johan
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D009707:Nucleosomes / Q000235:genetics* / Q000276:immunology*
D001323:Autoantibodies; D009707:Nucleosomes