Amoura Zahir, Piette Jean-Charles
Service de Médecine Interne, Hôpital Pitié-Salpêtrière, 47-83, boulevard de l'Hôpital, 75651 Paris Cedex 13.
Ann Med Interne (Paris). 2003 Feb;154(1):25-32.
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.
迄今越来越多的证据表明,核小体作为染色质的基本单位和细胞凋亡的普遍产物,在系统性红斑狼疮(SLE)的发病机制中起关键作用。核小体在SLE的抗核抗体反应中起核心作用。狼疮抗双链DNA抗体和抗组蛋白抗体针对核小体,与核小体特异性抗体一起属于广泛的抗核小体抗体家族。除抗双链DNA外,核小体特异性抗体在SLE的病理生理学中起主要作用,并突出了核小体-抗核小体免疫复合物的作用。抗核小体IgG抗体是比抗双链DNA更敏感的SLE标志物。高水平的抗核小体IgG几乎仅在SLE中发现。抗核小体IgG3与SLE疾病活动指数密切相关。核小体可结合多种细胞类型的表面并介导抗核小体抗体的结合。对核小体关键作用的理解为SLE开辟了新的治疗干预途径,例如对亚核小体颗粒的耐受性诱导。