Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, China.
Beijing Key Laboratory of Emerging Infectious Diseases, Capital Medical University, China.
Clin Infect Dis. 2020 Apr 15;70(9):1941-1949. doi: 10.1093/cid/ciz553.
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.
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.
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. A high level of cfDNA (>711.7 ng/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).
This study has a high degree of clinical impact for identification of cfDNA as a useful predictive biomarker of clinical outcomes of SFTS.
严重发热伴血小板减少综合征（SFTS）具有广泛的地理分布和高死亡率，对公共卫生构成了重大威胁。中性粒细胞胞外诱捕网（NETs）可被多种病原体激活，并与病毒感染中的血小板减少有关。我们旨在确定 NET 的产生及其对 SFTS 患者疾病进展和预后的预测价值。
对 112 例 SFTS 患者的多中心队列进行前瞻性研究，以定量检测血清 NET 水平。采用 PicoGreen 双链 DNA 检测法和酶联免疫吸附试验（ELISA）检测三种 NET 标志物，即无细胞游离 DNA（cfDNA）、髓过氧化物酶-DNA 复合物和乳铁蛋白-DNA 复合物。进行受试者工作特征曲线和多变量回归分析，以计算 cfDNA 水平的预测价值。
SFTS 的特征是明显的 NET 形成。NET 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呈负相关。高水平的 cfDNA 与多种病理过程密切相关，包括凝血障碍、心肌损伤、肝功能障碍和脑病的发生。初始诊断时 cfDNA 水平较高（>711.7ng/mL）强烈提示 SFTS 患者病情严重（优势比，8.285[95%置信区间，2.049-33.503]；P=0.003）。
本研究高度提示 cfDNA 作为 SFTS 临床结局的有用预测生物标志物的临床意义。
