[Immunology in medical practice. III. Disseminated lupus erythematosus: disturbed apoptosis?].
The main feature of systemic lupus erythematosus (SLE) is formation of antinuclear antibodies, particularly against double-stranded (ds) DNA. This autoimmune response is T cell- and (auto)antigen-dependent, but dsDNA is very poorly immunogenic. Recent data suggest that the nucleosome is the principal autoantigen in SLE. DNA is present in the circulation of SLE patients in the form of nucleosomes. In vivo, nucleosomes can only be generated through apoptosis. There is increasing evidence that apoptosis is disturbed in murine and human SLE. Nucleosomes have a high affinity for heparan sulphate in the glomerular basement membrane. By forming complexes with nucleosomes, antinuclear antibodies (both nucleosome-specific and anti-dsDNA autoantibodies) acquire a high affinity for the glomerular basement membrane, an initial key event in the development of lupus nephritis.
Berden
J H
JH
Academisch Ziekenhuis, afd. Nierziekten, Nijmegen.
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000936:Antigen-Antibody Complex / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D003429:Cross Reactions; D004247:DNA / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology; D051379:Mice; D009707:Nucleosomes / Q000276:immunology
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D009707:Nucleosomes; D004247:DNA