Pedersen Hege Lynum, Horvei Kjersti Daae, Thiyagarajan Dhivya, Seredkina Natalya, Rekvig Ole Petter
RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
RNA and Molecular Pathology Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
Semin Nephrol. 2015 Sep;35(5):427-38. doi: 10.1016/j.semnephrol.2015.08.004.
Lupus nephritis is one of the most serious manifestations of systemic lupus erythematosus, and represents one of the criteria implemented to classify systemic lupus erythematosus. Although studied for decades, no consensus has been reached related to the basic cellular, molecular, and immunologic mechanism(s) responsible for lupus nephritis. No causal treatments have been developed; therapy is approached mainly with nonspecific immunosuppressive medications. More detailed insight into disease mechanisms therefore is indispensable to develop new therapeutic strategies. In this review, contemporary knowledge on the pathogenic mechanisms of lupus nephritis is discussed based on recent data in murine and human lupus nephritis. Specific focus is given to the effect of anti-double-stranded DNA/antinucleosome antibodies in the kidneys and whether they bind exposed chromatin fragments in glomeruli or whether they bind inherent glomerular structures by cross-recognition. Overall, the data presented here favor the exposed chromatin model because we did not find any indication to substantiate the anti-double-stranded DNA antibody cross-reacting model. At the end of this review we present data on why chromatin fragments are expressed in the glomeruli of patients with lupus nephritis, and discuss how this knowledge can be used to direct the development of future therapies.
狼疮性肾炎是系统性红斑狼疮最严重的表现之一，也是用于系统性红斑狼疮分类的标准之一。尽管已经研究了数十年，但对于狼疮性肾炎的基本细胞、分子和免疫机制尚未达成共识。尚未开发出有因果关系的治疗方法；治疗主要采用非特异性免疫抑制药物。因此，更深入地了解疾病机制对于开发新的治疗策略必不可少。在这篇综述中，我们根据小鼠和人类狼疮性肾炎的最新数据，讨论了狼疮性肾炎致病机制的当代知识。特别关注抗双链DNA/抗核小体抗体在肾脏中的作用，以及它们是结合肾小球中暴露的染色质片段，还是通过交叉识别结合固有肾小球结构。总体而言，此处呈现的数据支持暴露染色质模型，因为我们没有发现任何证据支持抗双链DNA抗体交叉反应模型。在这篇综述的结尾，我们展示了关于染色质片段为何在狼疮性肾炎患者的肾小球中表达的数据，并讨论了如何利用这些知识指导未来治疗方法的开发。
