巖藻糖基化IgG與COVID-19嚴重程度相關
作者:
小柯機器人發布時間:2020/12/25 15:18:18
荷蘭阿姆斯特丹大學Gestur Vidarsson小組發現,巖藻糖基化IgG與COVID-19嚴重程度相關。相關論文於2020年12月23日在線發表在《科學》雜誌上。
研究人員發現,巖藻糖基化的IgG(約佔人類總IgG的6%)是針對包膜病毒而形成的,但通常不針對其他抗原。這可介導更強的Fc受體(FcγRIIIa)反應,但也會放大細胞因子風暴和免疫產生的病理。重症COVID-19患者,而非輕症患者,具有較高水平的SARS-CoV-2巖藻糖基化IgG抗體,從而放大了促炎性細胞因子的釋放和急性期反應。因此,抗體糖基化在包膜病毒(包括COVID-19)的免疫反應中起關鍵作用。
據了解,IgG抗體對於防禦入侵的病原體至關重要。IgG功能必需的IgG-Fc尾巴中高度保守的N-連接聚糖在人體內顯示出可變的組成。巖藻糖基化的IgG變體通過FcγRIIIa增強了活性,並已用於抗癌治療性抗體中。
附:英文原文
Title: Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity
Author: 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, Toni uti, 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- biobank study group, Theo Rispens, Jeroen den Dunnen, Hans L. Zaaijer, Manfred Wuhrer, C. Ellen van der Schoot, Gestur Vidarsson
Issue&Volume: 2020/12/23
Abstract: IgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG (~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 levels of afucosylated IgG antibodies against SARS-CoV-2, amplifying pro-inflammatory cytokine release and acute phase responses. Thus, antibody glycosylation plays a critical role in immune responses to enveloped viruses, including COVID-19.
DOI: 10.1126/science.abc8378
Source: https://science.sciencemag.org/content/early/2020/12/22/science.abc8378
Science:《科學》,創刊於1880年。隸屬於美國科學促進會,最新IF:41.037