Banerjee Arup, Shukla Shweta, Pandey Abhay Deep, Goswami Saptamita, Bandyopadhyay Bhaswati, Ramachandran Vishnampettai, Das Shukla, Malhotra Arjun, Agarwal Amitesh, Adhikari Srima, Rahman Mehebubar, Chatterjee Shatakshee, Bhattacharya Nemai, Basu Nandita, Pandey Priyanka, Sood Vikas, Vrati Sudhanshu
Vaccine and Infectious Disease Research Center (VIDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, India.
University College of Medical Sciences (UCMS) & Guru Teg Bahadur (GTB) Hospital, Delhi, Delhi, India.
Transl Res. 2017 Aug;186:62-78.e9. doi: 10.1016/j.trsl.2017.06.007. Epub 2017 Jun 17.
Patients infected with Dengue virus usually present a mild, self-limiting febrile dengue infection (DI) that occasionally leads to a potentially lethal complication, called the severe dengue (DS). The ability to identify the prognostic markers of DS could allow an improved disease intervention and management. To identify the transcriptional signatures associated with the dengue disease progression, we carried out the high-throughput sequencing of the RNA isolated from the peripheral blood mononuclear cells (PBMCs) of the dengue patients of varying severity and compared with that in the patients with other febrile illnesses (OFIs) or the healthy controls. The transcriptional signatures that discriminated the DS patients from OFI and DI patients were broadly related to the pathways involving glycine, serine, and threonine metabolisms, extracellular matrix organization, ubiquitination, and cytokines and inflammatory response. Several upregulated genes in the inflammatory process (MPO, DEFA4, ELANE, AUZ1, CTSG, OLFM4, SLC16A14, and CRISP3) that were associated with the dengue disease progression are known to facilitate leukocyte-mediated migration, and neutrophil activation and degranulation process. High activity of MPO and ELANE in the plasma samples of the follow-up and recovered dengue patients, as well as and the presence of a larger amount of cell-free dsDNA in the DS patients, suggested an association of neutrophil-mediated immunity with dengue disease progression. Careful monitoring of some of these gene transcripts, and control of the activity of proteins encoded by them, may have a great translational significance for the prognosis and management of the dengue patients.
感染登革病毒的患者通常表现为轻度、自限性的发热性登革热感染（DI），偶尔会导致一种潜在致命的并发症，即重症登革热（DS）。识别重症登革热的预后标志物有助于改善疾病的干预和管理。为了识别与登革热疾病进展相关的转录特征，我们对不同严重程度的登革热患者外周血单核细胞（PBMC）分离出的RNA进行了高通量测序，并与其他发热性疾病（OFI）患者或健康对照进行比较。区分重症登革热患者与发热性疾病患者和登革热感染患者的转录特征广泛涉及甘氨酸、丝氨酸和苏氨酸代谢、细胞外基质组织、泛素化以及细胞因子和炎症反应等途径。炎症过程中几个上调的基因（MPO、DEFA4、ELANE、AUZ1、CTSG、OLFM4、SLC16A14和CRISP3）与登革热疾病进展相关，已知这些基因有助于白细胞介导的迁移以及中性粒细胞的激活和脱颗粒过程。随访和康复的登革热患者血浆样本中MPO和ELANE的高活性，以及重症登革热患者中存在大量游离双链DNA，表明中性粒细胞介导的免疫与登革热疾病进展有关。仔细监测其中一些基因转录本，并控制它们所编码蛋白质的活性，可能对登革热患者的预后和管理具有重要的转化意义。
