Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity
Author:
Larsen Mads Delbo12ORCID, de Graaf Erik L.12ORCID, Sonneveld Myrthe E.12, Plomp H. Rosina3ORCID, Nouta Jan3, Hoepel Willianne45ORCID, Chen Hung-Jen67ORCID, Linty Federica12, Visser Remco12ORCID, Brinkhaus Maximilian12, Šuštić Tonći12ORCID, de Taeye Steven W.12ORCID, Bentlage Arthur E. H.12ORCID, Toivonen Suvi8ORCID, Koeleman Carolien A. M.3, Sainio Susanna8, Kootstra Neeltje A.9, Brouwer Philip J. M.9ORCID, Geyer Chiara Elisabeth45ORCID, Derksen Ninotska I. L.102ORCID, Wolbink Gertjan11ORCID, de Winther Menno67ORCID, Sanders Rogier W.912ORCID, van Gils Marit J.9ORCID, de Bruin Sanne13, Vlaar Alexander P. J.13ORCID, Rispens Theo102ORCID, den Dunnen Jeroen45ORCID, Zaaijer Hans L.14ORCID, Wuhrer Manfred3ORCID, Ellen van der Schoot C.12, Vidarsson Gestur12ORCID, van Agtmael Michiel, Algera Anne Geke, van Baarle Frank, Bax Diane, van de Beek Diederik, Beudel Martijn, Bogaard Harm Jan, Bonta Peter I., Bomers Marije, Bos Lieuwe, Botta Michela, de Bree Godelieve, Brouwer Matthijs C., Brabander Justin, de Bruin Sanne, Bugiani Marianna, Bulle Esther, Chouchane Osoul, Cloherty Alex, Elbers Paul, Fleuren Lucas, Geerlings Suzanne, Geerts Bart, Geijtenbeek Theo, Girbes Armand, Goorhuis Bram, Grobusch Martin P., Hafkamp Florianne, Hagens Laura, Hamann Jorg, Harris Vanessa, Hemke Robert, Hermans Sabine M., Heunks Leo, Hollmann Markus W., Horn Janneke, Hovius Joppe W., de Jong Menno, Koning Rutger, van Mourik Niels, Nellen Jeaninne, Nossent Esther J., Paulus Frederique, Peters Edgar, van der Poll Tom, Preckel Bennedikt, Prins Jan M., Raasveld Jorinde, Rijnders Tom, Schinkel Michiel, Schultz Marcus, Schuurmans Alex R., Sigaloff Kim, Smit Marry, Stijnis Cornelis S., Stilma Willemke, Teunissen Charlotte, Thoral Patrick, Tsonas Anissa, van der Valk Marc, Veelo Denise, Vlaar Alexander P. J., de Vries Heder, van Vugt Michèle, Wiersinga W. Joost, Wouters Dorien, Zwinderman A. H. (Koos), ,
Affiliation:
1. Department of Experimental Immunohematology, Sanquin Research, Amsterdam, Netherlands. 2. Landsteiner Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 3. Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands. 4. Department of Rheumatology and Clinical Immunology, Amsterdam UMC, Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands. 5. Department of Experimental Immunology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 6. Department of Medical Biochemistry, Experimental Vascular Biology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands. 7. Department of Cardiovascular Sciences, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands. 8. Finnish Red Cross Blood Service, Helsinki, Finland. 9. Department of Medical Microbiology, Amsterdam UMC, Amsterdam Infection and Immunity Institute, University of Amsterdam, Amsterdam, Netherlands. 10. Department of Immunopathology, Sanquin Research, Amsterdam, Netherlands. 11. Amsterdam Rheumatology and Immunology Center, Reade, Amsterdam, Netherlands. 12. Weill Medical College, Cornell University, New York, USA. 13. Department of Intensive Care Medicine, Amsterdam UMC (Location AMC), University of Amsterdam, Amsterdam, Netherlands. 14. Department of Blood-borne Infections, Sanquin, Amsterdam, Netherlands.
Abstract
A single sugar makes all the difference
Antibodies are divided into several classes based on their nonvariable tail (Fc) domains. These regions interact with disparate immune cell receptors and complement proteins to help instruct distinct immune responses. The Fc domain of immunoglobulin G (IgG) antibodies contains a conserved N-linked glycan at position 297. However, the particular glycan used at this position is highly variable. IgG lacking core fucosylation at this position initiates enhanced antibody-dependent cellular cytotoxicity by increased affinity to the Fc receptor FcRIIIa. Larsen
et al.
report that COVID-19 patients with severe symptoms have increased levels of anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG afucosylation compared with patients with mild disease. These findings suggest that treatment of COVID-19 patients with fucosylated anti–SARS-CoV-2 antibodies may circumvent pathologies associated with severe COVID-19.
Science
, this issue p.
eabc8378
Funder
Landsteiner Foundation for Blood Transfusion Research H2020 European Research Council Seventh Framework Programme ZonMW Amsterdam Infection and Immunity Institute Netherlands Organization for Scientific Research Marie Skłodowska-Curie
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Multidisciplinary
Cited by
238 articles.
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