Stephanou A, Latchman D S, Isenberg D A
Department of Molecular Pathology, University College London, UK.
Semin Arthritis Rheum. 1998 Dec;28(3):155-62. doi: 10.1016/s0049-0172(98)80032-2.
After a serendipitous suggestion, it was established that a significant subset of patients with systemic lupus erythematosus (SLE) overexpress the 90-kD heat shock protein (Hsp90). In this review, we have analyzed our own data and that of others, to explore the link between Hsp90 and SLE.
We performed a detailed literature review focusing on the potential role of Hsp in the etiopathogenesis of SLE.
Data are discussed showing surface expression of this Hsp in patients with lupus, a similar overexpression in the splenocytes of MRL/Ipr mice before the onset of disease, the detection of antibodies to Hsp90 in a proportion of both lupus patients and lupus-prone mice, and most recently, an analysis of the transcription factors that regulate the production of this protein and the influence of key cytokines on these factors.
These observations provide a model to show how a protein with key physiological roles in healthy individuals may, on occasion, become the target of an autoimmune attack with clinical consequences recognized in both mouse and human. Given that up to now, other heat shock proteins are not targeted in a similar fashion, the specificity of these responses is remarkable.
在一个意外的建议之后，发现系统性红斑狼疮（SLE）患者中有相当一部分子集过度表达90-kD热休克蛋白（Hsp90）。在本综述中，我们分析了我们自己和其他人的数据，以探索Hsp90与SLE之间的联系。
我们进行了详细的文献综述，重点关注Hsp在SLE发病机制中的潜在作用。
讨论了相关数据，显示狼疮患者中这种Hsp的表面表达、疾病发作前MRL/Ipr小鼠脾细胞中类似的过度表达、一部分狼疮患者和狼疮易感小鼠中Hsp90抗体的检测，以及最近对调节该蛋白产生的转录因子和关键细胞因子对这些因子的影响的分析。
这些观察结果提供了一个模型，展示了在健康个体中具有关键生理作用的蛋白质如何偶尔成为自身免疫攻击的目标，并在小鼠和人类中产生临床后果。鉴于到目前为止，其他热休克蛋白没有以类似方式成为靶点，这些反应的特异性非常显著。
