Nature Communications (Jan 2024)

IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

  • Benjamin S. Haslund-Gourley,
  • Kyra Woloszczuk,
  • Jintong Hou,
  • Jennifer Connors,
  • Gina Cusimano,
  • Mathew Bell,
  • Bhavani Taramangalam,
  • Slim Fourati,
  • Nathan Mege,
  • Mariana Bernui,
  • Matthew C. Altman,
  • Florian Krammer,
  • Harm van Bakel,
  • IMPACC Network,
  • Holden T. Maecker,
  • Nadine Rouphael,
  • Joann Diray-Arce,
  • Brian Wigdahl,
  • Michele A. Kutzler,
  • Charles B. Cairns,
  • Elias K. Haddad,
  • Mary Ann Comunale

DOI
https://doi.org/10.1038/s41467-023-44211-0
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 19

Abstract

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Abstract The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.