Journal Article

Glycosylation signature of plasma IgA of critically ill COVID-19 patients

Wygrecka, Małgorzata, Falck, David, Bertrams, Wilhelm, Mack, Elisabeth, Zlatina, Kristina, Schaefer, Liliana, Potaczek, Daniel P., Seeger, Werner, David, Sascha, Krolczik, Christina, Schmeck, Bernd, van Tol, Bianca D. M., Galuska, Sebastian P., Skevaki, Chrysanthi, Seeliger, Benjamin, Wuhrer, Manfred, Wilhelm, Jochen

2024

Overview

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.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Adult / Aged / Anticoagulants / Antigens / ARDS / Chromatography / COVID-19 / COVID-19 - blood / COVID-19 - immunology / Critical Illness / Female / Glycosylation / Humans / Immune response / Immunoglobulin A / Immunoglobulin A - blood / Immunoglobulin A - immunology / Immunology / Immunomodulation / Infectious diseases / Influenza / Influenza A / Influenza, Human - blood / Influenza, Human - immunology / Leukocytes (neutrophilic) / Male / Middle Aged / N-glycans / NETosis / Neutrophils / Peptides / Plasma / Polysaccharides / Polysaccharides - blood / Polysaccharides - immunology / Respiratory distress syndrome / Respiratory Distress Syndrome - blood / Respiratory Distress Syndrome - immunology / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Thromboembolism