Nucleosomes in the pathogenesis of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is characterized by the development of a large array of autoantibodies that primarily are directed against the whole chromatin (antinucleosome) and its individual components, dsDNA and histones. Apoptotic defects and impaired removal of apoptotic cells could contribute to an overload of autoantigens (and in particular of nucleosomes) in circulation or in target tissues that could become available to initiate an autoimmune response. In susceptible individuals, this can lead to autoantibody-mediated tissue damage. In addition to intrinsic or secondary apoptosis/apoptotic cell removal defects, certain apoptotic stimuli (eg, UV, viruses) could lead to posttranscriptional modifications that generate autoantigen cryptic fragments for which cells of the immune system have not been tolerized. Besides their role as a major immunogen in lupus, nucleosomes participate in antibody-mediated renal pathogenicity and act as a bridging molecule that recognizes heparin sulfate/collagen V components of the glomerular basement membrane. New tools that were developed to detect antinucleosome antibodies in the serum of patients (by ELISA) have shown the specificity and the high sensitivity of antinucleosome antibody reactivity in SLE. In particular, antinucleosome could be a useful marker of patients who have SLE and lack anti-dsDNA antibodies, a prognosis marker for imminent relapse, and a diagnosis marker of lupus nephritis.
Koutouzov
Sophie
S
Institut des Cytokines Paris-Sud, INSERM U131, 32 Rue des Carnets, 92140 Clamart, France. sophie.koutouzov@inserm.ipsc.u-sud.fr
Jeronimo
Antonio L
AL
Campos
Henri
H
Amoura
Zahir
Z
D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D009707:Nucleosomes / Q000235:genetics / Q000276:immunology*
D001324:Autoantigens; D009707:Nucleosomes