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

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; Theo Rispens; Jeroen den Dunnen; Hans L Zaaijer; Manfred Wuhrer; C Ellen van der Schoot; Gestur Vidarsson; Amsterdam UMC COVID-19; M Bugiani

doi:10.1126/science.abc8378

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

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 DerksenGertjan Wolbink, Menno de Winther, Rogier W Sanders, Marit J van Gils, Sanne de Bruin, Alexander P J Vlaar, Theo Rispens, Jeroen den Dunnen, Hans L Zaaijer, Manfred Wuhrer, C Ellen van der Schoot, Gestur Vidarsson, Amsterdam UMC COVID-19, M Bugiani

Research output: Contribution to journal › Article › Academic › peer-review

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 (FcgRIIIa). 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 FcgRIIIa 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.

Original language	English
Article number	abc8378
Journal	Science
Volume	371
Issue number	6532
DOIs	https://doi.org/10.1126/science.abc8378
Publication status	Published - 26 Feb 2021

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Larsen, M. D., de Graaf, E. L., Sonneveld, M. E., Plomp, H. R., Nouta, J., Hoepel, W., Chen, H-J., Linty, F., Visser, R., Brinkhaus, M., Šuštić, T., de Taeye, S. W., Bentlage, A. E. H., Toivonen, S., Koeleman, C. A. M., Sainio, S., Kootstra, N. A., Brouwer, P. J. M., Geyer, C. E., ... Bugiani, M. (2021). Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity. Science, 371(6532), [abc8378]. https://doi.org/10.1126/science.abc8378

@article{a544be552caa4e3aa83d4b9124499775,

title = "Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity",

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 (FcgRIIIa). 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 FcgRIIIa 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.",

author = "Larsen, {Mads Delbo} and {de Graaf}, {Erik L} and Sonneveld, {Myrthe E} and Plomp, {H Rosina} and Jan Nouta and Willianne Hoepel and Hung-Jen Chen and Federica Linty and Remco Visser and Maximilian Brinkhaus and Ton{\'c}i {\v S}u{\v s}ti{\'c} and {de Taeye}, {Steven W} and Bentlage, {Arthur E H} and Suvi Toivonen and Koeleman, {Carolien A M} and Susanna Sainio and Kootstra, {Neeltje A} and Brouwer, {Philip J M} and Geyer, {Chiara Elisabeth} and Derksen, {Ninotska I L} and Gertjan Wolbink and {de Winther}, Menno and Sanders, {Rogier W} and {van Gils}, {Marit J} and {de Bruin}, Sanne and Vlaar, {Alexander P J} and Theo Rispens and {den Dunnen}, Jeroen and Zaaijer, {Hans L} and Manfred Wuhrer and {Ellen van der Schoot}, C and Gestur Vidarsson and {Amsterdam UMC COVID-19} and M Bugiani",

year = "2021",

month = feb,

day = "26",

doi = "10.1126/science.abc8378",

language = "English",

volume = "371",

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issn = "0036-8075",

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Larsen, MD, de Graaf, EL, Sonneveld, ME, Plomp, HR, Nouta, J, Hoepel, W, Chen, H-J, Linty, F, Visser, R, Brinkhaus, M, Šuštić, T, de Taeye, SW, Bentlage, AEH, Toivonen, S, Koeleman, CAM, Sainio, S, Kootstra, NA, Brouwer, PJM, Geyer, CE, Derksen, NIL, Wolbink, G, de Winther, M, Sanders, RW, van Gils, MJ, de Bruin, S, Vlaar, APJ, Rispens, T, den Dunnen, J, Zaaijer, HL, Wuhrer, M, Ellen van der Schoot, C, Vidarsson, G, Amsterdam UMC COVID-19 & Bugiani, M 2021, 'Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity', Science, vol. 371, no. 6532, abc8378. https://doi.org/10.1126/science.abc8378

TY - JOUR

T1 - Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity

AU - Larsen, Mads Delbo

AU - de Graaf, Erik L

AU - Sonneveld, Myrthe E

AU - Plomp, H Rosina

AU - Nouta, Jan

AU - Hoepel, Willianne

AU - Chen, Hung-Jen

AU - Linty, Federica

AU - Visser, Remco

AU - Brinkhaus, Maximilian

AU - Šuštić, Tonći

AU - de Taeye, Steven W

AU - Bentlage, Arthur E H

AU - Toivonen, Suvi

AU - Koeleman, Carolien A M

AU - Sainio, Susanna

AU - Kootstra, Neeltje A

AU - Brouwer, Philip J M

AU - Geyer, Chiara Elisabeth

AU - Derksen, Ninotska I L

AU - Wolbink, Gertjan

AU - de Winther, Menno

AU - Sanders, Rogier W

AU - van Gils, Marit J

AU - de Bruin, Sanne

AU - Vlaar, Alexander P J

AU - Rispens, Theo

AU - den Dunnen, Jeroen

AU - Zaaijer, Hans L

AU - Wuhrer, Manfred

AU - Ellen van der Schoot, C

AU - Vidarsson, Gestur

AU - Amsterdam UMC COVID-19

AU - Bugiani, M

PY - 2021/2/26

Y1 - 2021/2/26

N2 - 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 (FcgRIIIa). 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 FcgRIIIa 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.

AB - 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 (FcgRIIIa). 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 FcgRIIIa 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.

UR - http://www.scopus.com/inward/record.url?scp=85099867645&partnerID=8YFLogxK

U2 - 10.1126/science.abc8378

DO - 10.1126/science.abc8378

M3 - Article

C2 - 33361116

VL - 371

JO - Science

JF - Science

SN - 0036-8075

IS - 6532

M1 - abc8378

ER -

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

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