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

Nat Commun. 2024 Jan 9;15(1):404. doi: 10.1038/s41467-023-44211-0.

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.

MeSH terms

  • COVID-19*
  • Complement System Proteins
  • Glycosylation
  • Glycosyltransferases
  • Humans
  • Immunoglobulin M
  • SARS-CoV-2

Substances

  • Glycosyltransferases
  • Complement System Proteins
  • Immunoglobulin M