[Role of the nucleosome in the physiopathology of systemic lupus erythematosus].
Evidence is to date accumulating to suggest that the nucleosome, the fundamental unit of chromatin and ubiquitous product of cell apoptosis, plays a key role in the pathogeny of systemic lupus erythematosus (SLE). Nucleosomes play a central role in the antinuclear antibody response in SLE. Lupus anti-dsDNA and antihistone antibodies are directed towards nucleosomes and belong together with nucleosome-specific antibodies to a broad anti-nucleosome antibody family. Besides anti-dsDNA, nucleosome-specific antibodies have a major role in the pathophysiology of SLE and emphazise the role of nucleosome-antinucleosome immune complexes. Antinucleosome IgG antibodies are a more sensitive marker of SLE than anti-dsDNA. High levels of antinucleosome IgG are almost exclusively found in SLE. Antinucleosome IgG3 are strongly correlated with the SLE disease activity index. Nucleosome can bind to the surface of several cell types and mediate the binding of antinucleosome antibodies. Understanding of the key role of the nucleosome has opened new therapeutic intervention in SLE, such a tolerance induction to the subnucleosomal particles.
Service de Médecine Interne, Hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75651 Paris Cedex 13. zahir.amoura@psl.ap-hop-paris.fr
Zahir
Z
Amoura
Jean-Charles
JC
Piette
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D004247:DNA / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D006657:Histones / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology / Q000503:physiopathology* / Q000628:therapy; D008181:Lupus Nephritis / Q000209:etiology / Q000276:immunology; D051379:Mice; D009707:Nucleosomes / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D000939:Epitopes; D006657:Histones; D007074:Immunoglobulin G; D009707:Nucleosomes; D004247:DNA