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Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity
Science ( IF 41.845 ) Pub Date : 2021-02-26 , DOI: 10.1126/science.abc8378
Mads Delbo Larsen, Erik L. de Graaf, Myrthe E. Sonneveld, H. Rosina Plomp, Jan Nouta, Willianne Hoepel, Hung-Jen Chen, Federica Linty, Remco Visser, Maximilian Brinkhaus, Tonći Šuštić, Steven W. de Taeye, Arthur E. H. Bentlage, Suvi Toivonen, Carolien A. M. Koeleman, Susanna Sainio, Neeltje A. Kootstra, Philip J. M. Brouwer, Chiara Elisabeth Geyer, Ninotska I. L. Derksen, Gertjan Wolbink, Menno de Winther, Rogier W. Sanders, Marit J. van Gils, Sanne de Bruin, Alexander P. J. Vlaar, Amsterdam UMC COVID-19, biobank study group†, Theo Rispens, Jeroen den Dunnen, Hans L. Zaaijer, Manfred Wuhrer, C. Ellen van der Schoot, Gestur Vidarsson

Immunoglobulin G (IgG) antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, which is essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anticancer therapeutic antibodies for their increased activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (approximately 6% of total IgG in humans) are specifically formed against enveloped viruses but generally not against other antigens. This mediates stronger FcγRIIIa responses but also amplifies brewing cytokine storms and immune-mediated pathologies. Critically ill COVID-19 patients, but not those with mild symptoms, had high concentrations of afucosylated IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), amplifying proinflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.



中文翻译:

无岩藻糖基化的IgG表征包膜病毒反应并与COVID-19严重程度相关

免疫球蛋白G(IgG)抗体对于防止入侵的病原体至关重要。IgG-Fc尾部中高度保守的N-连接聚糖(对IgG功能至关重要)在人体内显示出可变的组成。岩藻糖基化的IgG变体已通过Fc受体(FcγRIIIa)增强了活性,已用于抗癌治疗性抗体中。在这里,我们报道岩藻糖基化的IgG(约占人类总IgG的6%)是针对包膜病毒而形成的,但通常不针对其他抗原。这会介导更强的FcγRIIIa反应,但也会放大酿造细胞因子风暴和免疫介导的病理。重症COVID-19患者(而非轻症患者)具有针对严重急性呼吸系统综合症冠状病毒2(SARS-CoV-2)的岩藻糖基化IgG抗体,增强促炎细胞因子的释放和急性期反应。因此,抗体糖基化在对包膜病毒包括COVID-19的免疫反应中起关键作用。

更新日期:2021-02-26
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