Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity
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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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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 Statement Consent: 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.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources n=24 Live Attenuated vaccine) and HBV antibodies (n=17 natural infection, n=16 HBsAg vaccination) HBVsuggested: NonePurification of CMV-specific antibodies from sera: … 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 Statement Consent: 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.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources n=24 Live Attenuated vaccine) and HBV antibodies (n=17 natural infection, n=16 HBsAg vaccination) HBVsuggested: NonePurification 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 IgGsuggested: NonePurification 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 IgGsuggested: NoneMumps IgGsuggested: NoneAs 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-HIVsuggested: NoneIgG1suggested: NonePurification 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-Nsuggested: Noneanti-Ssuggested: NonePurification 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 antibodiessuggested: NoneTotal IgG1suggested: NoneBriefly , 1suggested: NoneMass 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-specificsuggested: Nonetotal IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources 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). HEKsuggested: NoneSoftware and Algorithms Sentences Resources 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 Programsuggested: NoneMass 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. Skylinesuggested: (Skyline, RRID:SCR_014080)Statistical analysis: Statistical analyses were performed using GraphPad Prism version 7.02 for Windows (GraphPad Software Inc., GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (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.
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