Cucunawangsih Cucunawangsih, Sari-Wijaya Ratna, Hardjo-Lugito Nata Pratama, Suriapranata Ivet
Department of Microbiology, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia.
Department of Internal Medicine, Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia.
J Arthropod Borne Dis. 2024 Jun 30;18(2):172-179. doi: 10.18502/jad.v18i2.17540. eCollection 2024 Jun.
The spectrum of dengue infection ranges from asymptomatic or mild to severe disease. The pathogenic mechanisms are not fully understood. A viral infection can induce the neutrophil extracellular traps (NETs), and the excessive NETs lead to increased vascular permeability, coagulopathy, and platelet dysfunction, a hallmark of severe dengue.
To evaluate the association of NETs formation with disease severity using a human public transcriptomic dataset (GSE17924) and clinical samples from dengue patients with different disease severity.
Based on the transcriptomic analysis, the whole blood gene expression functional in neutrophil activities and NETs formation was upregulated with dengue disease severity. The serum concentration of citrullinated histone H3 (CitH3), a NETs marker, was measured in 28 dengue patients, of whom 18 classified as dengue fever (DF) and 10 as dengue hemorrhagic fever (DHF) grade 1 and 2. A significantly higher CitH3 concentration was found in DHF compared to DF patients. The level of CitH3 was negatively correlated with platelet counts.
Our results suggest NETs have contributed to the disease severity of dengue infection. Future studies on the predictive value of NETs markers and the potential NETs as a targeted therapy in dengue disease should be prioritized.
登革热感染的范围从无症状或轻症到重症疾病。其致病机制尚未完全明确。病毒感染可诱导中性粒细胞胞外诱捕网（NETs）形成，而过多的NETs会导致血管通透性增加、凝血病和血小板功能障碍，这是重症登革热的一个标志。
利用人类公共转录组数据集（GSE17924）和来自不同疾病严重程度的登革热患者的临床样本，评估NETs形成与疾病严重程度之间的关联。
基于转录组分析，随着登革热疾病严重程度的增加，全血中与中性粒细胞活性和NETs形成相关的基因表达上调。对28例登革热患者检测了NETs标志物瓜氨酸化组蛋白H3（CitH3）的血清浓度，其中18例为登革热（DF），10例为1级和2级登革出血热（DHF）。与DF患者相比，DHF患者的CitH3浓度显著更高。CitH3水平与血小板计数呈负相关。
我们的结果表明NETs促成了登革热感染的疾病严重程度。未来应优先开展关于NETs标志物预测价值以及将NETs作为登革热疾病靶向治疗的潜在研究。
