Immunoglobulin G1 Fc glycosylation as an early hallmark of severe COVID-19.
Pongracz, T; Nouta, J; Wang, Wenjun; van, Meijgaarden KE; Linty, F; Vidarsson, G; Joosten, SA; Ottenhoff, THM; Hokke, CH; de, Vries JJC; Arbous, SM; Roukens, AHE; groups, COVID-19
(2022) EBioMedicine, volume 78, issue April 01
(Article)
Abstract
Background: Immunoglobulin G1 (IgG1) effector functions are impacted by the structure of fragment crystallizable (Fc) tail-linked N-glycans. Low fucosylation levels on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein-specific IgG1 has been described as a hallmark of severe coronavirus disease 2019 (COVID-19) and may lead to activation of
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macrophages via immune complexes thereby promoting inflammatory responses, altogether suggesting involvement of IgG1 Fc glycosylation modulated immune mechanisms in COVID-19. Methods: In this prospective, observational single center cohort study, IgG1 Fc glycosylation was analyzed by liquid chromatography-mass spectrometry following affinity capturing from serial plasma samples of 159 SARS-CoV-2 infected hospitalized patients. Findings: At baseline close to disease onset, anti-S IgG1 glycosylation was highly skewed when compared to total plasma IgG1. A rapid, general reduction in glycosylation skewing was observed during the disease course. Low anti-S IgG1 galactosylation and sialylation as well as high bisection were early hallmarks of disease severity, whilst high galactosylation and sialylation and low bisection were found in patients with low disease severity. In line with these observations, anti-S IgG1 glycosylation correlated with various inflammatory markers. Interpretation: Association of low galactosylation, sialylation as well as high bisection with disease severity and inflammatory markers suggests that further studies are needed to understand how anti-S IgG1 glycosylation may contribute to disease mechanism and to evaluate its biomarker potential. Funding: This project received funding from the European Commission's Horizon2020 research and innovation program for H2020-MSCA-ITN IMforFUTURE, under grant agreement number 721815, and supported by Crowdfunding Wake Up To Corona, organized by the Leiden University Fund.
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Keywords: Anti-spike IgG, COVID-19, Coronavirus, IgG glycosylation, SARS-CoV-2, General Biochemistry,Genetics and Molecular Biology
ISSN: 2352-3964
Publisher: Elsevier BV
Note: Funding Information: This project received funding from the European Commission's Horizon 2020 research and innovation program for H2020-MSCA-ITN IMforFUTURE, under grant agreement number 721815, and supported by Crowdfunding Wake Up To Corona, organized by the Leiden University Fund. Funding Information: The datasets generated for this study are available on request from the corresponding author. B. M. van den Berg2, S. Cannegieter3, C. M. Cobbaert4, A. van der Does5, J. J. M. van Dongen6, H. C. J. Eikenboom7, M. C. M. Feltkamp8, A. Geluk9, J. J. Goeman10, M. Giera11, T. Hankemeier12, M. H. M. Heemskerk13, P. S. Hiemstra5, J. J. Janse14, S. P. Jochems14, M. Kikkert8, L. Lamont12, J. Manni?n10, M. R. del Prado1, N. Queralt Rosinach15, M. Roestenberg14, M. Roos15, H. H. Smits14, E. J. Snijder8, F. J. T. Staal6, L. A. Trouw6, R. Tsonaka10, A. Verhoeven11, L. G. Visser9, D. J. van Westerloo1, J. Wigbers1, H. J. van der Wijk10, R. C. van Wissen4, M. Yazdanbakhsh14, M. Zlei6, 1Department of Intensive Care, Leiden University Medical Center, Leiden, Netherlands, 2Department of Internal Medicine, Nephrology, Leiden University Medical Center, Leiden, Netherlands, 2Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands, 4Department of Clinical Chemistry, Leiden University Medical Center, Leiden, Netherlands, 5Department of Pulmonary Medicine, Leiden University Medical Center, Leiden, Netherlands, 6Department of Immunology, Leiden University Medical Center, Leiden, Netherlands, 7Department of Internal Medicine, Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, Netherlands, 8Department of Medical Microbiology, Leiden University Medical Center, Leiden, Netherlands, 9Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands, 10Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, Netherlands, 11Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands, 12Department of Analytical Biosciences, Leiden Academic Centre for Drug Research, Leiden, Netherlands, 13Department of Hematology, Leiden University Medical Center, Leiden, Netherlands, 14Department of Parasitology, Leiden University Medical Center, Leiden, Netherlands, 15Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands, M. Baysan2,3, M. G. J. de Boer4, A. G. van der Bom3, O. M. Dekkers3, A. M. Eikenboom3, S. B. ter Haar3, L. Heerdink3, L. J. van Heurn3, I. de Jonge3, W. Lijfering3, R. Meier1, J. A. Oud1, F. Rosendaal3, A. G. L. Toppenberg3, J. Uzorka4, A. A. van Ijlzinga Veenstra, J. Wigbers2, J. M. Wubbolts4, 1Department of Hematology, Leiden University Medical Center, Leiden, Netherlands, 2Department of Intensive Care, Leiden University Medical Center, Leiden, Netherlands, 3Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands, 4Department of Infectious Diseases, Leiden University Medical Center, Leiden, Netherlands, This project received funding from the European Commission's Horizon 2020 research and innovation program for H2020-MSCA-ITN IMforFUTURE, under grant agreement number 721815, and supported by Crowdfunding Wake Up To Corona, organized by the Leiden University Fund. Publisher Copyright: © 2022 The Author(s)
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