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登革热感染住院患儿疾病严重程度的血清免疫生物标志物。

Serological immune biomarker for disease severity in dengue-infected pediatric hospitalized patients.

机构信息

Department of Molecular Medicine, Jamia Hamdard, Hamdard Nagar, New Delhi, India.

Department of Paediatrics, Hamdard Institute of Medical Sciences and Research, Jamia Hamdard, New Delhi, India.

出版信息

J Med Virol. 2024 Jul;96(7):e29779. doi: 10.1002/jmv.29779.

DOI:10.1002/jmv.29779
PMID:38975640
Abstract

Clinical manifestation of dengue disease ranges from asymptomatic, febrile fever without warning sign (DOS) to serious outcome dengue with warning sign (DWS) and severe disease (SD) leading to shock syndrome and death. The role of antibody response in natural dengue infection is complex and not completely understood. Here, we aimed to assess serological marker for disease severity. Antibody response of dengue-confirmed pediatric patients with acute secondary infection were evaluated against infecting virus, immature virus, and recombinant envelop protein. Immature virus antibody titers were significantly higher in DWS as compared to DOS (p = 0.0006). However, antibody titers against recombinant envelop protein were higher in DOS as compared to DWS, and antibody avidity was significantly higher against infecting virus in DOS. Serum samples of DOS patients displayed higher in vitro neutralization potential in plaque assay as compared to DWS, whereas DWS serum samples showed higher antibody-dependent enhancement in the in vitro enhancement assays. Thus, antibodies targeting immature virus can predict disease severity and could be used in early forecast of disease outcome using an enzyme-linked immunoassay assay system which is less laborious and cheaper than plaque assay system for correlates of protection and could help optimize medical care and resources.

摘要

登革热疾病的临床表现从无症状、无预警发热(DOS)到有预警症状的严重登革热(DWS)和严重疾病(SD),导致休克综合征和死亡。抗体反应在自然登革热感染中的作用是复杂的,尚未完全理解。在这里,我们旨在评估血清学标志物与疾病严重程度的关系。评估了急性二次感染的登革热确诊儿科患者对感染病毒、不成熟病毒和重组包膜蛋白的抗体反应。与 DOS 相比,DWS 中的不成熟病毒抗体滴度明显更高(p=0.0006)。然而,DOS 中的重组包膜蛋白抗体滴度高于 DWS,DOS 中针对感染病毒的抗体亲和力明显更高。与 DWS 相比,DOS 患者的血清样本在斑块测定中的体外中和潜力更高,而 DWS 血清样本在体外增强测定中的抗体依赖性增强更高。因此,针对不成熟病毒的抗体可以预测疾病的严重程度,并可用于使用酶联免疫吸附试验(ELISA)检测系统进行早期疾病结局预测,该系统比斑块测定系统更省力、更便宜,可用于保护相关因素的检测,并有助于优化医疗保健和资源的利用。

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