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

Autor:	Larsen MD; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., de Graaf EL; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Sonneveld ME; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Plomp HR; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Nouta J; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Hoepel W; Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Chen HJ; Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; Department of Cardiovascular Sciences, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands., Linty F; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Visser R; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Brinkhaus M; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Šuštić T; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., de Taeye SW; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Bentlage AEH; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Toivonen S; Finnish Red Cross Blood Service, Helsinki, Finland., Koeleman CAM; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Sainio S; Finnish Red Cross Blood Service, Helsinki, Finland., Kootstra NA; Department of Medical Microbiology, Amsterdam UMC, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands., Brouwer PJM; Department of Medical Microbiology, Amsterdam UMC, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands., Geyer CE; Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Derksen NIL; Department of Immunopathology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Wolbink G; Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, Netherlands., de Winther M; Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; Department of Cardiovascular Sciences, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands., Sanders RW; Department of Medical Microbiology, Amsterdam UMC, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands.; Weill Medical College, Cornell University, New York, USA., van Gils MJ; Department of Medical Microbiology, Amsterdam UMC, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands., de Bruin S; Department of Intensive Care Medicine, Amsterdam UMC (Location AMC), University of Amsterdam, Amsterdam, Netherlands., Vlaar APJ; Department of Intensive Care Medicine, Amsterdam UMC (Location AMC), University of Amsterdam, Amsterdam, Netherlands., Rispens T; Department of Immunopathology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., den Dunnen J; Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands.; Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Zaaijer HL; Department of Blood-borne Infections, Sanquin, Amsterdam, Netherlands., Wuhrer M; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands., Ellen van der Schoot C; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands., Vidarsson G; Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands. g.vidarsson@sanquin.nl.; Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	Science (New York, N.Y.) [Science] 2021 Feb 26; Vol. 371 (6532). Date of Electronic Publication: 2020 Dec 23.
DOI:	10.1126/science.abc8378
Abstrakt:	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. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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