在寡头，聚节少年性特发性关节炎和肠炎相关关节炎的嗜中性粒细胞外陷阱形成：用于诊断和疾病活动的生物标志物
Increased neutrophil extracellular trap formation in oligoarticular, polyarticular juvenile idiopathic arthritis and enthesitis-related arthritis: biomarkers for diagnosis and disease activity
影响因子:5.90000
分区:医学2区 / 免疫学2区
发表日期:2024
作者:
Hongxia Tang, Yucheng Zhong, Yali Wu, Yanmei Huang, Yi Liu, Jing Chen, Ting Xi, Yini Wen, Ting He, Shanshan Yang, Fan Liu, Runji Xiong, Runming Jin
摘要
中性粒细胞外陷阱（网）是引发和永久炎症的重要因素。然而，很少研究网中网中网中幼体特发性关节炎（JIA）的作用。因此，我们的目的是探索贾雅衍生的中性粒细胞释放网的能力，以及TNF-α（肿瘤坏死因子 - α）抑制剂对体外和体内净形成的影响，并评估净衍生产物与临床和免疫范围的网络效果的关联。通过体外刺激和抑制研究。检测到血浆网衍生的产品以评估体内净形成的发生率。此外，使用流式细胞仪和蛋白质印迹来检测嗜中性粒细胞中的网络相关信号传导成分。与源自HCS的患者相比，源自HCS的嗜中性粒细胞，具有寡头性jia的患者，多关节性jia和enthisisisitis炎的关节炎，与Prolate Contrate and Nets and vents and-Pmame and Prone and Prone and Prone and Prone and Prone and tnnf。 JIA患者的周围循环中存在过多的净形成，并且血浆水平升高的净衍生产物（无细胞DNA和MPO-DNA复合物）可以准确地将JIA患者与HCS区分开，并与疾病活性呈正相关。多线性回归分析表明，红细胞沉积速率和TNF-α水平是自变量，并且与无细胞的DNA浓度正相关。值得注意的是，TNF-α抑制剂可以有效地防止体外和体内净形成。此外，在JIA来源的中性粒细胞中与网络相关激酶的磷酸化水平显着增加。我们的数据表明，网络可能扮演致病作用，并且可能参与JIA的TNF-α介导的炎症。循环网衍生产品具有潜在的诊断和疾病监测价值。此外，与JIA患者净形成的分子机制有关的初步结果为净靶向治疗提供了理论上的基础。
Abstract
Neutrophil extracellular traps (NETs) are important factors in initiating and perpetuating inflammation. However, the role of NETs in different subtypes of juvenile idiopathic arthritis (JIA) has been rarely studied. Therefore, we aimed to explore the ability of JIA-derived neutrophils to release NETs and the effect of TNF-α (tumor necrosis factor-alpha) inhibitors on NET formation both in vitro and in vivo, and evaluate the associations of NET-derived products with clinical and immune-related parameters.The ability of neutrophils to release NETs and the effect of adalimumab on NET formation was assessed via in vitro stimulation and inhibition studies. Plasma NET-derived products were detected to assess the incidence of NET formation in vivo. Furthermore, flow cytometry and western blotting were used to detect NET-associated signaling components in neutrophils.Compared to those derived from HCs, neutrophils derived from patients with oligoarticular-JIA, polyarticular-JIA and enthesitis-related arthritis were more prone to generate NETs spontaneously and in response to TNF-α or PMA in vitro. Excessive NET formation existed in peripheral circulation of JIA patients, and elevated plasma levels of NET-derived products (cell-free DNA and MPO-DNA complexes) could accurately distinguish JIA patients from HCs and were positively correlated with disease activity. Multiple linear regression analysis showed that erythrocyte sedimentation rate and TNF-α levels were independent variables and were positively correlated with cell-free DNA concentration. Notably, TNF-α inhibitors could effectively prevent NET formation both in vitro and in vivo. Moreover, the phosphorylation levels of NET-associated kinases in JIA-derived neutrophils were markedly increased.Our data suggest that NETs might play pathogenic roles and may be involved in TNF-α-mediated inflammation in JIA. Circulating NET-derived products possess potential diagnostic and disease monitoring value. Furthermore, the preliminary results related to the molecular mechanisms of NET formation in JIA patients provide a theoretical basis for NET-targeted therapy.