Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India.
Department of Tropical Medicine, Infectious Diseases & Advanced Microbiology, Calcutta School of Tropical Medicine, Kolkata, West Bengal, India.
J Med Virol. 2023 Oct;95(10):e29180. doi: 10.1002/jmv.29180.
Dengue virus (DENV) induced severe manifestations is a precursor for fatality among infected patients. Previous autopsy examinations of severe dengue (SD) patients reported presence of apoptotic cells in liver, brain, intestinal and lung tissues. Thus, serum-level of major apoptotic proteins of dengue patients was evaluated in the current study, along with their biochemical parameters. Patients were categorized according to World Health Organization (WHO)-defined classification. DENV-infection was screened among 165 symptomatic patients by quantitative reverse transcription polymerase chain reaction, antidengue IgM, and IgG ELISA. Serum levels of apoptotic (Capase-3,7,8, Bcl-2 and FasL) and hepatic-markers, lipid profile, hematological parameters of 78 dengue-positive patients were determined by sandwich-ELISA/immunoturbidimetry/auto-analyzer. Significantly higher levels of caspase-3,7,8 and FasL was detected among SD patients compared to those without warning (WOW) signs. Amongst biochemical parameters, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase serum concentrations significantly increased among severe patients. Principal component analysis followed by hierarchical clustering differentiated severe and with warning dengue patient groups from those WOW using caspase-3,7,8 and FasL biomarkers-thus clearly distinguishing severe-dengue group. Correlation analyses also established strong positive correlation between caspase-3,7,8 and FasL. Thus, serum level of caspase-3,7,8 and FasL during early stage of infection could be used as biomarkers for WHO-defined dengue disease severity.
登革病毒(DENV)引起的严重表现是感染患者死亡的前兆。先前对重症登革热(SD)患者的尸检检查报告称,在肝、脑、肠和肺组织中存在凋亡细胞。因此,本研究评估了登革热患者血清中主要凋亡蛋白的水平及其生化参数。根据世界卫生组织(WHO)定义的分类对患者进行分类。通过定量逆转录聚合酶链反应、抗登革热 IgM 和 IgG ELISA 对 165 例有症状患者进行了 DENV 感染筛查。通过夹心 ELISA/免疫比浊法/自动分析仪测定了 78 例登革热阳性患者的凋亡(Capase-3、7、8、Bcl-2 和 FasL)和肝标志物、血脂谱、血液学参数。与无警告(WOW)迹象的患者相比,SD 患者的 caspase-3、7、8 和 FasL 水平明显更高。在生化参数中,胆红素、天门冬氨酸氨基转移酶、丙氨酸氨基转移酶、碱性磷酸酶血清浓度在重症患者中显著升高。主成分分析和层次聚类使用 caspase-3、7、8 和 FasL 生物标志物将重症和有警告的登革热患者与 WOW 患者区分开来,从而明确区分重症登革热组。相关性分析还建立了 caspase-3、7、8 和 FasL 之间的强正相关。因此,感染早期血清中 caspase-3、7、8 和 FasL 的水平可作为 WHO 定义的登革热疾病严重程度的生物标志物。