Lupus nephritis: consequence of disturbed removal of apoptotic cells?
In the last decade it has become clear that systemic lupus erythematosus (SLE) is an autoantigen driven T cell dependent autoimmune disease. The nucleosome has been identified as a major autoantigen. Nucleosomes are generated during apoptosis. Either an increased or delayed apoptosis or a reduced clearance of apoptotic cells (which are not mutually exclusive) leads to an increased exposure of (modified, more immunogenic) nucleosomes to the immune system. This generates the formation of nucleosome specific T cells and antinucleosome autoantibodies. After complex formation of antinucleosome or anti-double-stranded (ds)DNA antibodies with nucleosomes, these autoantibodies are targeted to basement membranes, especially the glomerular basement membrane (GBM). This nephritogenic potential is due to the binding of the positively charged histone components of the nucleosome to the negatively charged heparan sulphate (HS) within the GBM. This incites glomerular inflammation.
Berden
J H M
JH
Nephrology Research Laboratory, Nijmegen Centre for Molecular Life Sciences and Division of Nephrology (545), University Medical Centre St Radboud, PO Box 9101, 6500 HB Nijmegen, The Netherlands. J.Berden@nier.umcn.nl
D000974:Antibodies, Antinuclear / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D006801:Humans; D008181:Lupus Nephritis / Q000276:immunology* / Q000503:physiopathology*; D009707:Nucleosomes / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology
D000974:Antibodies, Antinuclear; D009707:Nucleosomes