Reference Database

Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity.
Larsen, Mads Delbo
de Graaf, Erik L
Sonneveld, Myrthe E
Plomp, H Rosina
Nouta, Jan
Hoepel, Willianne
Chen, Hung-Jen
Linty, Federica
Visser, Remco
Brinkhaus, Maximilian
Šuštić, Tonći
de Taeye, Steven W
Bentlage, Arthur E H
Toivonen, Suvi
Koeleman, Carolien A M
Sainio, Susanna
Kootstra, Neeltje A
Brouwer, Philip J M
Geyer, Chiara Elisabeth
Derksen, Ninotska I L
Wolbink, Gertjan
de Winther, Menno
Sanders, Rogier W
van Gils, Marit J
de Bruin, Sanne
Vlaar, Alexander P J
Amsterdam UMC COVID-19 biobank study group
Rispens, Theo
den Dunnen, Jeroen
Zaaijer, Hans L
Wuhrer, Manfred
Ellen van der Schoot, C
Vidarsson, Gestur
Science (New York, N.Y.) 2020 Dec 23;371 (6532): eabc8378

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.

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