| Literature DB >> 33361116 |
Mads Delbo Larsen1,2, Erik L de Graaf1,2, Myrthe E Sonneveld1,2, H Rosina Plomp3, Jan Nouta3, Willianne Hoepel4,5, Hung-Jen Chen6,7, Federica Linty1,2, Remco Visser1,2, Maximilian Brinkhaus1,2, Tonći Šuštić1,2, Steven W de Taeye1,2, Arthur E H Bentlage1,2, Suvi Toivonen8, Carolien A M Koeleman3, Susanna Sainio8, Neeltje A Kootstra9, Philip J M Brouwer9, Chiara Elisabeth Geyer4,5, Ninotska I L Derksen10,2, Gertjan Wolbink11, Menno de Winther6,7, Rogier W Sanders9,12, Marit J van Gils9, Sanne de Bruin13, Alexander P J Vlaar13, Theo Rispens10,2, Jeroen den Dunnen4,5, Hans L Zaaijer14, Manfred Wuhrer3, C Ellen van der Schoot1,2, Gestur Vidarsson15,2.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2020 PMID： 33361116 PMCID： PMC7919849 DOI： 10.1126/science.abc8378
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728