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

IMPACC Data Analysis Group, IMPACC Site Investigators, IMPACC Core Laboratory, IMPACC Clinical Study Team, IMPACC Network, IMPACC Steering Committee, Clinical & Data Coordinating Center (CDCC)

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number404
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

Fingerprint

Dive into the research topics of 'IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition'. Together they form a unique fingerprint.

Cite this