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.

• Potaczek, D. P.
• van Tol, B. D. M.
• Falck, D.
• Krolczik, C.
• Zlatina, K.
• Bertrams, W.
• Wilhelm, J.
• Schmeck, B.
• Seeliger, B.
• David, S.
• Skevaki, C.
• Mack, E.
• Seeger, W.
• Schaefer, L.
• Galuska, S. P.
• Wuhrer, M.
• Wygrecka, M.