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抗体岩藻糖基化可预测继发性登革热感染的疾病严重程度
作者:小柯机器人 发布时间:2021/6/6 15:47:04

美国洛克菲勒大学Jeffrey V. Ravetch、柬埔寨巴斯德研究所Tineke Cantaert等研究人员合作发现,抗体岩藻糖基化可预测继发性登革热感染的疾病严重程度。该研究于2021年6月4日发表于国际一流学术期刊《科学》。

研究人员表示,尽管抗病毒抗体通常具有保护功能,但针对登革热病毒(DENV)的抗体与增强的疾病易感性有关。抗体可以通过Fcγ受体介导白细胞的DENV感染,这可能有助于登革热病的发病机制。

为了确定这种机制是否可以解释不同的疾病严重程度,研究人员检查了来自感染前后以及具有不同疾病结果患者的DENV抗体Fab和Fc结构。在DENV感染人群中,抗体滴度和中和活性均与疾病严重程度无关。相反,DENV感染会导致免疫球蛋白 G1(IgG1)岩藻糖基化的特定增加,并且岩藻糖化IgG1的水平可预测登革热病的严重程度。因此,IgG1岩藻糖基化状态是登革热疾病的强大预后工具,并突出了Fc聚糖结构在登革热发病机制中的关键作用。

附:英文原文

Title: Antibody fucosylation predicts disease severity in secondary dengue infection

Author: Stylianos Bournazos, Hoa Thi My Vo, Veasna Duong, Heidi Auerswald, Sowath Ly, Anavaj Sakuntabhai, Philippe Dussart, Tineke Cantaert, Jeffrey V. Ravetch

Issue&Volume: 2021/06/04

Abstract: Although antiviral antibodies generally confer protective functions, antibodies against dengue virus (DENV) are associated with enhanced disease susceptibility. Antibodies can mediate DENV infection of leukocytes via Fcγ receptors, likely contributing to dengue disease pathogenesis. To determine if this mechanism accounts for variable disease severity, we examined Fab and Fc structures of anti-DENV antibodies from patients before and after infection and with variable disease outcomes. Neither antibody titers nor neutralizing activity correlated with disease severity in DENV-infected populations. Rather, DENV infection induced a specific increase in immunoglobulin G1 (IgG1) afucosylation, and the levels of afucosylated IgG1 were predictive of dengue disease severity. Thus, the IgG1 fucosylation status represents a robust prognostic tool for dengue disease, highlighting the key role of the Fc glycan structure in dengue pathogenesis.

DOI: 10.1126/science.abc7303

Source: https://science.sciencemag.org/content/372/6546/1102

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037