{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T03:57:56Z","timestamp":1793937476230,"version":"4.8.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1439248","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T10:55:56Z","timestamp":1729767356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Glycosylation signature of plasma IgA of critically ill COVID-19 patients"],"prefix":"10.3389","volume":"15","author":[{"given":"Daniel P.","family":"Potaczek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca D. M.","family":"van Tol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Falck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Krolczik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Zlatina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Bertrams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Wilhelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Schmeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Seeliger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sascha","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chrysanthi","family":"Skevaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Mack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Seeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian P.","family":"Galuska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Wuhrer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Wygrecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2020-216243","article-title":"COVID-19, immunothrombosis and venous thromboembolism: biological mechanisms","volume":"76","author":"Loo","year":"2021","journal-title":"Thorax"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e2250010","DOI":"10.1002\/eji.202250010","article-title":"Neutrophil activation and neutrophil extracellular traps (NETs) in COVID-19 ARDS and immunothrombosis","volume":"53","author":"Cesta","year":"2023","journal-title":"Eur J Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2101497118","article-title":"IgA potentiates NETosis in response to viral infection","volume":"118","author":"Stacey","year":"2021","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/cells9122676","article-title":"IgA2 antibodies against SARS-coV-2 correlate with NET formation and fatal outcome in severely diseased COVID-19 patients","volume":"9","author":"Staats","year":"2020","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02436","article-title":"Comparative glycomics of immunoglobulin A and G from saliva and plasma reveals biomarker potential","volume":"9","author":"Plomp","year":"2018","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.9b05722","article-title":"Simultaneous immunoglobulin A and G glycopeptide profiling for high-throughput applications","volume":"92","author":"Mom\u010dilovi\u0107","year":"2020","journal-title":"Anal Chem"},{"key":"B7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1038\/s41467-019-13992-8","article-title":"IgA subclasses have different effector functions associated with distinct glycosylation profiles","volume":"11","author":"Steffen","year":"2020","journal-title":"Nat Commun"},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-030-76912-3_14","article-title":"Immunoglobulin a glycosylation and its role in disease","volume-title":"Exp Suppl.","author":"Hansen","year":"2021"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/rcm.8606","article-title":"Quantitative determination of human IgA subclasses and their Fc-glycosylation patterns in plasma by using a peptide analogue internal standard and ultra-high-performance liquid chromatography\/triple quadrupole mass spectrometry","volume":"34","author":"Chen","year":"2020","journal-title":"Rapid Commun Mass Spectromet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0190967","article-title":"Serum galactose-deficient-IgA1 and IgG autoantibodies correlate in patients with IgA nephropathy","volume":"13","author":"Placzek","year":"2018","journal-title":"PloS One"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2018.05.016","article-title":"Aberrant glycosylation of the igA1 molecule in igA nephropathy","volume":"38","author":"Novak","year":"2018","journal-title":"Semin Nephrol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020081208","article-title":"and N-glycosylation of serum immunoglobulin A is associated with igA nephropathy and glomerular function","volume":"32","author":"Dotz","year":"2021","journal-title":"J Am Soc Nephrol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/biom13071106","article-title":"An integrated glycosylation signature of rheumatoid arthritis","volume":"13","author":"Mayboroda","year":"2023","journal-title":"Biomolecules"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.3c00260","article-title":"Immunoglobulin A glycosylation differs between crohn\u2019s disease and ulcerative colitis","volume":"22","author":"Clerc","year":"2023","journal-title":"J Proteome Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.838011","article-title":"NETosis and neutrophil extracellular traps in COVID-19: immunothrombosis and beyond","volume":"13","author":"Zhu","year":"2022","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2021004816","article-title":"Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19","volume":"6","author":"Wygrecka","year":"2022","journal-title":"Blood Adv"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc8378","article-title":"Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity","volume":"371","author":"Larsen","year":"2021","journal-title":"Science"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021011871","article-title":"Aberrant glycosylation of anti-SARS-CoV-2 spike IgG is a prothrombotic stimulus for platelets","volume":"138","author":"Bye","year":"2021","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(20)30121-1","article-title":"Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia","volume":"2","author":"McGonagle","year":"2020","journal-title":"Lancet Rheumatol"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Perez-Riverol","year":"2022","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1439248\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T10:55:58Z","timestamp":1729767358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1439248\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,24]]},"references-count":20,"alternative-id":["10.3389\/fimmu.2024.1439248"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1439248","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,24]]},"article-number":"1439248"}}