Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity.
Adult
Aged
Antibodies, Viral
/ blood
COVID-19
/ immunology
Cells, Cultured
Critical Illness
Cytomegalovirus
/ immunology
Female
Fucose
/ analysis
Glycosylation
HIV
/ immunology
Hepatitis B Vaccines
/ immunology
Humans
Immunoglobulin Fc Fragments
/ chemistry
Immunoglobulin G
/ blood
Inflammation
Interleukin-6
/ biosynthesis
Macrophages
/ immunology
Male
Middle Aged
Parvovirus B19, Human
/ immunology
SARS-CoV-2
/ immunology
Severity of Illness Index
Spike Glycoprotein, Coronavirus
/ immunology
Vaccines, Subunit
/ immunology
Young Adult
Journal
Science (New York, N.Y.)
ISSN: 1095-9203
Titre abrégé: Science
Pays: United States
ID NLM: 0404511
Informations de publication
Date de publication:
26 02 2021
26 02 2021
Historique:
received:
16
05
2020
revised:
12
10
2020
accepted:
18
12
2020
pubmed:
29
12
2020
medline:
6
3
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33361116
pii: science.abc8378
doi: 10.1126/science.abc8378
pmc: PMC7919849
pii:
doi:
Substances chimiques
Antibodies, Viral
0
Hepatitis B Vaccines
0
IL6 protein, human
0
Immunoglobulin Fc Fragments
0
Immunoglobulin G
0
Interleukin-6
0
Spike Glycoprotein, Coronavirus
0
Vaccines, Subunit
0
spike protein, SARS-CoV-2
0
Fucose
28RYY2IV3F
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Michiel van Agtmael
(M)
Anne Geke Algera
(AG)
Frank van Baarle
(F)
Diane Bax
(D)
Diederik van de Beek
(D)
Martijn Beudel
(M)
Harm Jan Bogaard
(HJ)
Peter I Bonta
(PI)
Marije Bomers
(M)
Lieuwe Bos
(L)
Michela Botta
(M)
Godelieve de Bree
(G)
Matthijs C Brouwer
(MC)
Justin Brabander
(J)
Sanne de Bruin
(S)
Marianna Bugiani
(M)
Esther Bulle
(E)
Osoul Chouchane
(O)
Alex Cloherty
(A)
Paul Elbers
(P)
Lucas Fleuren
(L)
Suzanne Geerlings
(S)
Bart Geerts
(B)
Theo Geijtenbeek
(T)
Armand Girbes
(A)
Bram Goorhuis
(B)
Martin P Grobusch
(MP)
Florianne Hafkamp
(F)
Laura Hagens
(L)
Jorg Hamann
(J)
Vanessa Harris
(V)
Robert Hemke
(R)
Sabine M Hermans
(SM)
Leo Heunks
(L)
Markus W Hollmann
(MW)
Janneke Horn
(J)
Joppe W Hovius
(JW)
Menno de Jong
(M)
Rutger Koning
(R)
Niels van Mourik
(N)
Jeaninne Nellen
(J)
Esther J Nossent
(EJ)
Frederique Paulus
(F)
Edgar Peters
(E)
Tom van der Poll
(T)
Bennedikt Preckel
(B)
Jan M Prins
(JM)
Jorinde Raasveld
(J)
Tom Rijnders
(T)
Michiel Schinkel
(M)
Marcus Schultz
(M)
Alex R Schuurmans
(AR)
Kim Sigaloff
(K)
Marry Smit
(M)
Cornelis S Stijnis
(CS)
Willemke Stilma
(W)
Charlotte Teunissen
(C)
Patrick Thoral
(P)
Anissa Tsonas
(A)
Marc van der Valk
(M)
Denise Veelo
(D)
Alexander P J Vlaar
(APJ)
Heder de Vries
(H)
Michèle van Vugt
(M)
W Joost Wiersinga
(WJ)
Dorien Wouters
(D)
A H Koos Zwinderman
(AHK)
Informations de copyright
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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