Glycosylation signature of plasma IgA of critically ill COVID-19 patients
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.
Authors
- Kristina Zlatina (ORCID: https://orcid.org/0000-0003-2912-3445)
- Liliana Schaefer (ORCID: https://orcid.org/0000-0002-3318-3005)
- Wilhelm Bertrams (ORCID: https://orcid.org/0000-0002-0180-2529)
- Sascha David (ORCID: https://orcid.org/0000-0002-8231-0461)
- Bianca D. M. van Tol (ORCID: https://orcid.org/0000-0001-7486-8652)
- Małgorzata Wygrecka (ORCID: https://orcid.org/0000-0002-3656-2932)
- Werner Seeger (ORCID: https://orcid.org/0000-0003-1946-0894)
- Benjamin Seeliger (ORCID: https://orcid.org/0000-0001-7373-752X)
- Elisabeth Mack (ORCID: https://orcid.org/0000-0003-4061-494X)
- Christina Krolczik
- Jochen Wilhelm
- David Falck (ORCID: https://orcid.org/0000-0003-3908-2376)
- Manfred Wuhrer (ORCID: https://orcid.org/0000-0002-0814-4995)
- Bernd Schmeck (ORCID: https://orcid.org/0000-0002-2767-3606)
- Sebastian P. Galuska (ORCID: https://orcid.org/0000-0001-5565-0252)
- Daniel P. Potaczek (ORCID: https://orcid.org/0000-0003-0324-8506)
- Chrysanthi Skevaki (ORCID: https://orcid.org/0000-0001-5194-5635)
Institutions
- Goethe University Frankfurt (DE)
- Philipps University of Marburg (DE)
- Leiden University Medical Center (NL)
- Medizinische Hochschule Hannover (DE)
- University Hospital of Zurich (CH)
- Netherlands Metabolomics Centre (NL)
- Research Institute for Farm Animal Biology (FBN) (DE)
- German Center for Lung Research (DE)
- Universities of Giessen and Marburg Lung Center (DE)
- Cardio-Pulmonary Institute (DE)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2024-10-24
- DOI
- https://doi.org/10.3389/fimmu.2024.1439248
- Citations
- 3
- Primary Topic
- Diabetes and associated disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.65