AUTHOR=Potaczek Daniel P. , van Tol Bianca D. M. , Falck David , Krolczik Christina , Zlatina Kristina , Bertrams Wilhelm , Wilhelm Jochen , Schmeck Bernd , Seeliger Benjamin , David Sascha , Skevaki Chrysanthi , Mack Elisabeth , Seeger Werner , Schaefer Liliana , Galuska Sebastian P. , Wuhrer Manfred , Wygrecka MaƂgorzata TITLE=Glycosylation signature of plasma IgA of critically ill COVID-19 patients JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1439248 DOI=10.3389/fimmu.2024.1439248 ISSN=1664-3224 ABSTRACT=

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.