High levels of circulating cell-free DNA are associated with a poor prognosis in patients with severe fever with thrombocytopenia syndrome
High levels of circulating cell-free DNA are associated with a poor prognosis in patients with severe fever with thrombocytopenia syndrome
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高水平的循环游离 DNA 与严重发热伴血小板减少综合征患者的不良预后相关
DOI：
10.1093/cid/ciz553
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Liuluan Zhu
中科院分区：
文献类型：
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作者：
Yue Zhang;Rui Song;Yi Shen;Yongxiang Zhao;Zhenghua Zhao;Tianli Fan;Xiaoyu Yang;Lin Wang;Wei Zhang;Chong Chen;Di Tian;Ying Wang;Jing Wen;Ziruo Ge;Xiaoli Yu;Li Liu;Yang Feng;Jianping Duan;Yanli Ma;Xingwang Li;Hui Zeng;Zhihai Chen;Liuluan Zhu
背景发热伴血小板减少综合征（SFTS）的广泛地理分布和高死亡率使其成为公共卫生的重要威胁。中性粒细胞胞外陷阱（NET）可被多种病原体激活，并与病毒感染中的血小板减少症有关。我们的目的是确定NET的生产及其对SFTS患者疾病进展和预后的预测价值。方法.对SFTS患者（n=112）的多中心队列进行了一项前瞻性研究，以定量血清NET水平。NET的三个标志物，即，无细胞DNA（cfDNA），髓过氧化物酶-DNA复合物，和乳铁蛋白-DNA复合物，与PicoGreen双链DNA测定和酶联免疫吸附测定进行了测量。进行受试者操作特征曲线和多变量回归分析以计算cfDNA水平的预测值。结果SFTS的特点是明显的NET形成。NET的血清水平在疾病进展过程中动态变化，与血小板和中性粒细胞水平的趋势相反。高cfDNA水平与多种病理过程密切相关，包括凝血病、心肌损伤、肝功能障碍和脑病的发展。初诊时cfDNA水平高（>711.7ng/mL）预示SFTS患者病情严重（优势比，8.285 [95%可信区间，2.049-33.503]; P= 0.003）。结论.该研究对于鉴定cfDNA作为SFTS临床结果的有用预测生物标志物具有高度的临床影响。
Background. The extensive geographical distribution and high mortality rate of severe fever with thrombocytopenia syndrome (SFTS) have made it an important threat to public health. Neutrophil extracellular traps (NETs) can be activated by a variety of pathogens and are associated with thrombocytopenia in viral infections. We aimed to identify NET production and its predictive value for disease progression and prognosis in patients with SFTS. Methods. A prospective study was performed with a multicenter cohort of patients with SFTS (n=112) to quantify serum NET levels. Three markers of NETs—namely, cell-free DNA (cfDNA), myeloperoxidase-DNA complexes, and lactoferrin-DNA complexes—were measured with PicoGreen double-stranded DNA assays and enzyme-linked immunosorbent assays. Receiver operating characteristic curves and multivariate regression analyses were performed to calculate the predictive value of cfDNA levels. Results. SFTS was characterized by pronounced NET formation. The serum levels of NETs changed dynamically during disease progression, with an inverse pattern of the trends of platelet and neutrophil levels. High cfDNA levels were strongly associated with multiple pathological processes, including coagulopathy, myocardial damage, liver dysfunction, and the development of encephalopathy. Ahigh level of cfDNA (>711.7ng/mL) at the time of the initial diagnosis predicted severe illness in patients with SFTS (odds ratio, 8.285 [95% confidence interval, 2.049–33.503]; P=.003). Conclusions. This study has a high degree of clinical impact for identification of cfDNA as a useful predictive biomarker of clinical outcomes of SFTS.