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

  1. Mads Delbo Larsen
  2. Erik L. de Graaf
  3. Myrthe E. Sonneveld
  4. H. Rosina Plomp
  5. Jan Nouta
  6. Willianne Hoepel
  7. Hung-Jen Chen
  8. Federica Linty
  9. Remco Visser
  10. Maximilian Brinkhaus
  11. Tonći Šuštić
  12. Steven W. de Taeye
  13. Arthur E. H. Bentlage
  14. Suvi Toivonen
  15. Carolien A. M. Koeleman
  16. Susanna Sainio
  17. Neeltje A. Kootstra
  18. Philip J. M. Brouwer
  19. Chiara Elisabeth Geyer
  20. Ninotska I. L. Derksen
  21. Gertjan Wolbink
  22. Menno de Winther
  23. Rogier W. Sanders
  24. Marit J. van Gils
  25. Sanne de Bruin
  26. Alexander P. J. Vlaar
  27. Amsterdam UMC COVID-19
  28. biobank study group
  29. Theo Rispens
  30. Jeroen den Dunnen
  31. Hans L. Zaaijer
  32. Manfred Wuhrer
  33. C. Ellen van der Schoot
  34. Gestur Vidarsson
  35. Michiel van Agtmael
  36. Anne Geke Algera
  37. Frank van Baarle
  38. Diane Bax
  39. Diederik van de Beek
  40. Martijn Beudel
  41. Harm Jan Bogaard
  42. Peter I. Bonta
  43. Marije Bomers
  44. Lieuwe Bos
  45. Michela Botta
  46. Godelieve de Bree
  47. Matthijs C. Brouwer
  48. Justin Brabander
  49. Sanne de Bruin
  50. Marianna Bugiani
  51. Esther Bulle
  52. Osoul Chouchane
  53. Alex Cloherty
  54. Paul Elbers
  55. Lucas Fleuren
  56. Suzanne Geerlings
  57. Bart Geerts
  58. Theo Geijtenbeek
  59. Armand Girbes
  60. Bram Goorhuis
  61. Martin P. Grobusch
  62. Florianne Hafkamp
  63. Laura Hagens
  64. Jorg Hamann
  65. Vanessa Harris
  66. Robert Hemke
  67. Sabine M. Hermans
  68. Leo Heunks
  69. Markus W. Hollmann
  70. Janneke Horn
  71. Joppe W. Hovius
  72. Menno de Jong
  73. Rutger Koning
  74. Niels van Mourik
  75. Jeaninne Nellen
  76. Esther J. Nossent
  77. Frederique Paulus
  78. Edgar Peters
  79. Tom van der Poll
  80. Bennedikt Preckel
  81. Jan M. Prins
  82. Jorinde Raasveld
  83. Tom Rijnders
  84. Michiel Schinkel
  85. Marcus Schultz
  86. Alex R. Schuurmans
  87. Kim Sigaloff
  88. Marry Smit
  89. Cornelis S. Stijnis
  90. Willemke Stilma
  91. Charlotte Teunissen
  92. Patrick Thoral
  93. Anissa Tsonas
  94. Marc van der Valk
  95. Denise Veelo
  96. Alexander P. J. Vlaar
  97. Heder de Vries
  98. Michèle van Vugt
  99. W. Joost Wiersinga
  100. Dorien Wouters
  101. A. H. (Koos) Zwinderman

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Abstract

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

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  1. Version published to 10.1126/science.abc8378
  2. ScreenIT

    SciScore for 10.1101/2020.05.18.099507: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: The ACS have been conducted in accordance with the ethical principles set out in the declaration of Helsinki and all participants provided written informed consent.
    IRB: The study was approved by the Academic Medical Center institutional Medical Ethics Committee of the University of Amsterdam.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    n=24 Live Attenuated vaccine) and HBV antibodies (n=17 natural infection, n=16 HBsAg vaccination)
    HBV
    suggested: None
    Purification of CMV-specific antibodies from sera: CMV-specific antibodies were purified using antigen-coated plates (Serion ELISA classic, Cytomegalovirus IgG, Würzburg, Germany).
    Serion ELISA classic , Cytomegalovirus IgG
    suggested: None
    Purification of Measle- and Mump-virus specific antibodies from sera: Ag-specific antibodies were purified using antigen-coated plates (Serion ELISA classic, Measles IgG and Mumps IgG, Würzburg, Germany).
    Serion ELISA classic , Measles IgG
    suggested: None
    Mumps IgG
    suggested: None
    As positive control, anti-HIV gp120 monoclonal was used (IgG1 b12; 100 µg purified antibody in PBS at 1 mg/ml; NIH Aids Reagent Program, La Jolla, CA, US).
    anti-HIV
    suggested: None
    IgG1
    suggested: None
    Purification of anti-N and anti-S specific antibodies from plasma: SARS-Cov-2-specific antibodies were purified using antigen-coated plates (NUCN, Roskilde, Denmark).
    anti-N
    suggested: None
    anti-S
    suggested: None
    Purification of total IgG from sera: Total IgG1 antibodies were captured from 2 µL of serum using Protein G Sepharose 4 Fast Flow beads (GE Healthcare, Uppsala, Sweden) in a 96-well filter plate (Millipore Multiscreen, Amsterdam, The Netherlands) as described previously (11) or by using Protein G cartridges on the AssayMAP Bravo (Agilent Technologies, Santa Clara, USA) Briefly, 1 µL serum diluted in PBS were applied to the cartridges, followed by washes of PBS, LC-MS pure water and finally eluted with formic acid (1%)
    sera: Total IgG1 antibodies
    suggested: None
    Total IgG1
    suggested: None
    Briefly , 1
    suggested: None
    Mass spectrometric IgG-Fc glycosylation analysis: Eluates containing either antigen-specific antibodies or total IgG were collected in V-bottom plates, dried by vacuum centrifugation for 2.5 hours at 50°C.
    antigen-specific
    suggested: None
    total IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Plates were coated (over-night, 4°C) with recombinant trimerized spike protein produced as described recently (28) or N protein (accession number MN908947, produced in HEK cells with HAVT20 leader peptide, 10xhis tag and a Brit tag as in (23)) in PBS(5 µg/mL and 1 µg/mL, respectively).
    HEK
    suggested: None
    Software and Algorithms
    SentencesResources
    As positive control, anti-HIV gp120 monoclonal was used (IgG1 b12; 100 µg purified antibody in PBS at 1 mg/ml; NIH Aids Reagent Program, La Jolla, CA, US).
    Aids Reagent Program
    suggested: None
    Mass spectrometry results were extracted and evaluated using FlexAnalysis software (Bruker Daltonics) for all samples except for the Measles virus, and Mumps virus cohorts that were analyzed with Skyline software.
    Skyline
    suggested: (Skyline, RRID:SCR_014080)
    Statistical analysis: Statistical analyses were performed using GraphPad Prism version 7.02 for Windows (GraphPad Software Inc.,
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.05.18.099507v1 on bioRxiv