Pathogenesis of kidney disease in systemic lupus erythematosus.
Pathogenesis of kidney disease in systemic lupus erythematosus.
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DOI：
10.1097/bor.0b013e32832efff1
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发表时间：
2009-09
影响因子：
5.1
通讯作者：
Fu SM
中科院分区：
文献类型：
--
作者：
Bagavant H;Fu SM
系统性自身免疫和组织对免疫损伤的反应是红斑狼疮肾脏受累的基础。在这篇综述中，我们讨论了最近的文献调查狼疮性肾小球肾炎的发病机制。在狼疮性肾小球肾炎中，肾小球免疫复合物被认为是肾脏疾病的主要介质。最近的研究表明，多种特异性的自身抗体参与免疫复合物的形成，沉积在肾脏中。T细胞、巨噬细胞和树突状细胞的肾浸润在狼疮性肾小球肾炎导致肾衰竭的进展中起主导作用。Toll样受体的激活调节自身抗体的产生和系统性干扰素应答。然而，肾小球细胞对免疫损伤的反应影响疾病的结果。此外，在狼疮性肾小球肾炎终末器官损害易感性的遗传学方面也有了新的发现。在疾病进展过程中，反映在基因表达谱中的不同肾小球反应为狼疮性肾小球肾炎进展和发作的诊断提供了潜在的标志物。此外，终末器官反应的研究为治疗干预提供了新的靶点。狼疮性肾小球肾炎是由多种特异性自身抗体介导的免疫复合物疾病的原型，其中之一是抗DNA。自发性系统性红斑狼疮的小鼠模型对于了解潜在疾病至关重要。最近的研究表明，除了全身性自身免疫，终末器官反应和终末器官对损伤的抵抗力也是决定疾病结局的关键。这一认识将影响系统性红斑狼疮新治疗方法的设计。
A combination of systemic autoimmunity and tissue response to immune injury underlie renal involvement in lupus erythematosus. In this review, we discuss recent literature investigating pathogenetic mechanisms of lupus glomerulonephritis. In lupus glomerulonephritis, glomerular immune complexes were believed to be the primary mediators of renal disease. Recent studies make it apparent that autoantibodies of multiple specificities participate in the formation of immune complexes, deposited in the kidneys. Renal infiltration by T cells, macrophages, and dendritic cells have a dominant role in the progression of lupus glomerulonephritis leading to renal failure. Activation of Toll-like receptors modulates autoantibody production and systemic interferon responses. However, glomerular cell responses to immune injury influence disease outcome. In addition, new insights on the genetics of susceptibility to end-organ damage in lupus glomerulonephritis have been discovered. Differential glomerular responses reflected in gene expression profiles during disease progression provide potential markers for diagnosis of lupus glomerulonephritis progression and flares. In addition, studies of end-organ responses provide new targets for therapeutic interventions. Lupus glomerulonephritis is a prototype of immune complex disease mediated by autoantibodies of multiple specificities, one of which is anti-DNA. Murine models of spontaneous systemic lupus erythematosus have been critical for understanding the underlying disease. Recent studies demonstrate that in addition to systemic autoimmunity, end-organ responses, and end-organ resistance to damage are also critical in determining disease outcome. This understanding should influence design of novel therapeutic approaches in systemic lupus erythematosus.