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Record W3117759033 · doi:10.1126/science.abc8378

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

2020· article· en· W3117759033 on OpenAlexaff
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, S Toivonen, Carolien A. M. Koeleman, Susanna Sainio, Neeltje A. Kootstra, Philip J. M. Brouwer, Chiara E. Geyer, Ninotska I. L. Derksen, Gertjan Wolbink, Menno P.J. 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, Michiel A. van Agtmael, Anna Geke Algera, Frank van Baarle, Diane Bax, Diederik van de Beek, Martijn Beudel, Harm Jan Bogaard, Peter I. Bonta, Marije K. Bomers, Lieuwe D. J. Bos, Michela Botta, Godelieve de Bree, Matthijs C. Brouwer, Justin de Brabander, Marianna Bugiani, Esther Bulle, Osoul Chouchane, Alex Cloherty, Paul Elbers, Lucas M. Fleuren, Suzanne E. Geerlings, Bart F. Geerts, Armand R. J. Girbes, Martin P. Grobusch, Florianne Hafkamp, Laura A. Hagens, Jörg Hamann, Vanessa Harris, Robert Hemke, Sabine Hermans, Leo Heunks, Markus W. Hollmann, Janneke Horn, Joppe W. Hovius, Menno D. de Jong, Rutger Koning, Niels van Mourik, Esther J. Nossent, Frederique Paulus, Edgar J.G. Peters, Tom van der Poll, Bennedikt Preckel, Jan M. Prins, Jorinde Raasveld, Tom Rijnders, Michiel Schinkel, Marcus J. Schultz, Alex Schuurmans, Kim Sigaloff, Marry R. Smit, Cornelis Stijnis, Willemke Stilma, Charlotte E. Teunissen, Patrick Thoral, Anissa M. Tsonas, Marc van der Valk, Denise P. Veelo, Heder de Vries, Michèle van Vugt, W. Joost Wiersinga, Dorien Wouters, A. H. Zwinderman

Bibliographic record

VenueScience · 2020
Typearticle
Languageen
FieldMedicine
TopicMonoclonal and Polyclonal Antibodies Research
Canadian institutionsInstitute of Infection and Immunity
FundersSeventh Framework ProgrammeHorizon 2020 Framework ProgrammeStichting Sanquin BloedvoorzieningNederlandse Organisatie voor Wetenschappelijk OnderzoekUniversiteit van AmsterdamRijksinstituut voor Volksgezondheid en MilieuEuropean CommissionZonMwH2020 European Research CouncilLandsteiner Foundation for Blood Transfusion Research
KeywordsCoronavirus disease 2019 (COVID-19)Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)2019-20 coronavirus outbreakVirologyBetacoronavirusImmunologyMedicineOutbreakInternal medicineDisease

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.052
GPT teacher head0.339
Teacher spread0.287 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations413
Published2020
Admission routes1
Has abstractyes

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