Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that primarily affects young women and causes a wide range of inflammatory manifestations. The hallmark of SLE is the production of antibodies to components of the cell nucleus (antinuclear antibodies or ANAs). These antibodies can bind to DNA, RNA and protein complexes with nucleic acids. Among ANAs, antibodies to DNA (anti‐DNA) are markers for classification and disease activity, waxing and waning in many patients. In the blood, anti‐DNA antibodies can bind DNA to form immune complexes with two distinct roles in pathogenesis: renal deposition to provoke nephritis and stimulation of cytokine production following uptake into innate immune cells and interaction with internal nucleic acid sensors. These sensors are part of an internal host defense system in the cell cytoplasm that can respond to DNA from infecting organisms; during cell stress, DNA from nuclear and mitochondrial sources can also trigger these sensors. The formation of immune complexes requires a source of extracellular DNA in an immunologically accessible form. As shown in in vivo and in vitro systems, extracellular DNA can emerge from dead and dying cells in both a free and particulate form. Neutrophils undergoing the process of NETosis can release DNA in mesh‐like structures called NETs (neutrophil extracellular traps). In SLE, therefore, the combination of ANAs and immunologically active DNA can create new structures which can promote inflammation throughout the body as well as drive organ inflammation and damage.

中文翻译：

---

抗核抗体和核分子在 SLE 发病机制中独特的相互作用

系统性红斑狼疮 (SLE) 是一种典型的自身免疫性疾病，主要影响年轻女性并引起广泛的炎症表现。 SLE 的特点是产生针对细胞核成分的抗体（抗核抗体或 ANA）。这些抗体可以结合 DNA、RNA 和蛋白质与核酸的复合物。在 ANA 中，DNA 抗体（抗 DNA）是许多患者的分类和疾病活动、消长的标记。在血液中，抗 DNA 抗体可以结合 DNA 形成免疫复合物，在发病机制中具有两种不同的作用：肾沉积引发肾炎，以及在吸收到先天免疫细胞并与内部核酸传感器相互作用后刺激细胞因子的产生。这些传感器是细胞质中宿主内部防御系统的一部分，可以对感染生物体的 DNA 做出反应；在细胞应激期间，来自细胞核和线粒体的 DNA 也可以触发这些传感器。免疫复合物的形成需要免疫学上可访问形式的细胞外 DNA 来源。如图所示体内和体外在系统中，细胞外 DNA 可以以游离形式和颗粒形式从死亡和垂死的细胞中产生。经历 NETosis 过程的中性粒细胞可以在称为 NET（中性粒细胞胞外陷阱）的网状结构中释放 DNA。因此，在 SLE 中，ANA 和免疫活性 DNA 的结合可以产生新的结构，从而促进全身炎症并导致器官炎症和损伤。