Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity

Larsen, M.D.; Graaf, E.L. de; Sonneveld, M.E.; Plomp, H.R.; Nouta, J.; Hoepel, W.; Chen, H.J.; Linty, F.; Visser, R.; Brinkhaus, M.; Sustic, T.; Taeye, S.W. de; Bentlage, A.E.H.; Toivonen, S.; Koeleman, C.A.M.; Sainio, S.; Kootstra, N.A.; Brouwer, P.J.M.; Geyer, C.E.; Derksen, N.I.L.; Wolbink, G.; Winther, M. de; Sanders, R.W.; Gils, M.J. van; Bruin, S. de; Vlaar, A.P.J.; Rispens, T.; Dunnen, J. den; Zaaijer, H.L.; Wuhrer, M.; Schoot, C.E.V.; Vidarsson, G.; Amsterdam UMC COVID-19 Biobank Stu

doi:doi:10.1126/science.abc8378

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 (Fc gamma RIIIa). 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 Fc gamma RIIIa 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...Show moreImmunoglobulin 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 (Fc gamma RIIIa). 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 Fc gamma RIIIa 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.Show less

Leiden University Scholarly Publications

View statistics

Documents

In Collections

Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity