Laboratory of Prenantal Medicine, Department of Biomedicine, University Clinics Basel, Basel, Switzerland; Department of Rheumatology, Kantonsspital Aarau, Aarau, Switzerland.
Laboratory of Prenantal Medicine, Department of Biomedicine, University Clinics Basel, Basel, Switzerland; University Women's Hospital, University Clinics Basel, Basel, Switzerland.
Front Pediatr. 2016 Sep 13;4:97. doi: 10.3389/fped.2016.00097. eCollection 2016.
Neutrophil extracellular trap (NET) formation represents a form of cell death distinct from apoptosis or necrosis, by which invading pathogens are simultaneously entangled and potentially eliminated. Increased NET formation is observed in systemic lupus erythematosus (SLE), rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated small vessel vasculitis, antiphospholipid antibody syndrome (APS), and psoriasis. NETs contribute to the pathogenesis of autoimmunity by exposing cryptic autoepitopes, which may facilitate the generation of autoantibodies, induce the production of interferons, and activate the complement cascade. In SLE, augmented disease activity and renal disease are associated with increased NET formation, so that NETs could serve as a marker for the monitoring of disease activity. NETs can additionally cause endothelial cell damage and death and stimulate inflammation in atheromatous plaques, adding to the accelerated atherosclerosis witnessed in autoimmune disease. Since NETs induce production of interferons, assessing the extent of NET formation might facilitate the prediction of IFN-alpha levels and identification of SLE patients with presumably better responses to anti-IFN-alpha therapies or other novel therapeutic concepts, such as N-acetyl-cysteine and inhibitors of DNase 1 and peptidylarginine deiminase 4 (PAD4), which also target NETs. In summary, the study of NETs provides a novel approach to the understanding of autoimmune disease pathogenesis in childhood and opens new vistas in the development of sensitive disease markers and targeted therapies.
中性粒细胞胞外诱捕网（NET）的形成代表了一种不同于细胞凋亡或坏死的细胞死亡形式，通过这种形式，入侵的病原体同时被纠缠并可能被消除。系统性红斑狼疮（SLE）、类风湿关节炎、抗中性粒细胞胞质抗体相关性小血管血管炎、抗磷脂抗体综合征（APS）和银屑病中观察到 NET 形成增加。NET 通过暴露隐匿自身表位来促进自身免疫的发病机制，这可能有助于产生自身抗体、诱导干扰素产生，并激活补体级联反应。在 SLE 中，增加的疾病活动度和肾脏疾病与 NET 形成增加有关，因此 NET 可作为监测疾病活动度的标志物。NET 还可以导致内皮细胞损伤和死亡，并在动脉粥样硬化斑块中刺激炎症，从而加速自身免疫疾病中观察到的动脉粥样硬化。由于 NET 诱导干扰素的产生，评估 NET 形成的程度可能有助于预测 IFN-α 水平，并识别出可能对 IFN-α 治疗或其他新型治疗概念（如 N-乙酰半胱氨酸和 DNA 酶 1 和肽基精氨酸脱亚氨酶 4（PAD4）抑制剂）有更好反应的 SLE 患者，这些概念也针对 NET。总之，NET 的研究为理解儿童自身免疫性疾病的发病机制提供了一种新方法，并为敏感疾病标志物和靶向治疗的发展开辟了新的前景。
