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BRIEF RESEARCH REPORT article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1439248
This article is part of the Research Topic Glycobiology and Glycosylation: Deciphering the Secrets of Glycans in Humans and Pathogens View all 7 articles

Brief research report: Glycosylation signature of plasma IgA of critically ill COVID-19 patients

Provisionally accepted
  • 1 Center for Infection and Genomics of the Lung (CIGL), Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, University of Giessen, Giessen, Germany
  • 2 Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden University, Leiden, Netherlands
  • 3 Research Institute for Farm Animal Biology, Dummerstorf, Germany
  • 4 Institute for Lung Research, Universities of Giessen and Marburg Lung Center, German Center for Lung Research (DZL), University of Marburg, Marburg, Hesse, Germany
  • 5 Institute for Lung Health (ILH), Member of the German Center for Lung Research, University of Giessen, Giessen, Germany
  • 6 Department of Respiratory Medicine, Hannover Medical School, Hanover, Lower Saxony, Germany
  • 7 Institute of Intensive Care, University Hospital Zürich, Zurich, Zürich, Switzerland
  • 8 Institute of Laboratory Medicine, University of Marburg, Marburg, Hesse, Germany
  • 9 Department of Hematology, Oncology and Immunology, University of Marburg, Marburg, Hesse, Germany
  • 10 Institute of Pharmacology and Toxicology, Goethe University Frankfurt, Frankfurt, Hesse, Germany

The final, formatted version of the article will be published soon.

    Thromboembolic complications are common in severe COVID-19 and are thought to result from excessive neutrophil-extracellular-trap (NET)-driven immunothrombosis. Glycosylation plays a vital role in the efficiency of immunoglobulin A (IgA) effector functions, with significant implications for NET formation in infectious diseases. This study represents the first comprehensive analysis of plasma IgA glycosylation during severe SARS-CoV-2 or Influenza A infection, revealing lower sialylation and higher galactosylation of IgA1 O-glycans in acute respiratory distress syndrome (ARDS), regardless of the underlying cause of the disease. Importantly, N-glycans displayed an infection-specific pattern, with N47 of IgA2 showing diminished sialylation and bisection, and N340/N327 of IgA1/2 demonstrating lower fucosylation and antennarity along with higher non-complex glycans in COVID-19 compared to Influenza. Notably, COVID-19 IgA possessed strong ability to induce NET formation and its glycosylation patterns correlated with extracellular DNA levels in plasma of critically ill COVID-19 patients. Our data underscores the necessity of further research on the role of IgA glycosylation in the modulation of pathogen-specific immune responses in COVID-19 and other infectious diseases.

    Keywords: ARDS, COVID-19, Glycosylation, Immunoglobulin A, NEtosis

    Received: 27 May 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Potaczek, van Tol, Falck, Krolczik, Zlatina, Bertrams, Wilhelm, Schmeck, Seeliger, David, Skevaki, Mack, Seeger, Schaefer, Galuska, Wuhrer and Wygrecka. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Malgorzata Wygrecka, Center for Infection and Genomics of the Lung (CIGL), Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, University of Giessen, Giessen, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.