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)

doi:10.1038/s41467-023-44211-0

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 journal › Article › peer-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 language	English (US)
Article number	404
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-44211-0
State	Published - Dec 2024

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-023-44211-0

Cite this

IMPACC Data Analysis Group, IMPACC Site Investigators, IMPACC Core Laboratory, IMPACC Clinical Study Team, IMPACC Network, IMPACC Steering Committee, & Clinical & Data Coordinating Center (CDCC) (2024). IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition. Nature communications, 15(1), Article 404. https://doi.org/10.1038/s41467-023-44211-0

IMPACC Data Analysis Group, IMPACC Site Investigators, IMPACC Core Laboratory, IMPACC Clinical Study Team, IMPACC Network, IMPACC Steering Committee & Clinical & Data Coordinating Center (CDCC) 2024, 'IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition', Nature communications, vol. 15, no. 1, 404. https://doi.org/10.1038/s41467-023-44211-0

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title = "IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition",

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.",

author = "{IMPACC Data Analysis Group} and {IMPACC Site Investigators} and {IMPACC Core Laboratory} and {IMPACC Clinical Study Team} and {IMPACC Network} and {IMPACC Steering Committee} and {Clinical & Data Coordinating Center (CDCC)} and Haslund-Gourley, {Benjamin S.} and Kyra Woloszczuk and Jintong Hou and Jennifer Connors and Gina Cusimano and Mathew Bell and Bhavani Taramangalam and Slim Fourati and Nathan Mege and Mariana Bernui and Altman, {Matthew C.} and Florian Krammer and {van Bakel}, Harm and Maecker, {Holden T.} and Nadine Rouphael and Joann Diray-Arce and Brian Wigdah and Kutzler, {Michele A.} and Cairns, {Charles B.} and Haddad, {Elias K.} and Comunale, {Mary Ann} and Al Ozonoff and Ehrlich, {Lauren I.R.} and Esther Melamed and Sesma, {Ana Fernandez} and Viviana Simon and Bali Pulendran and Nadeau, {Kari C.} and Davis, {Mark M.} and McCoey, {Grace A.} and Rafick Sekaly and Baden, {Lindsey R.} and Ofer Levy and Joanna Schaenman and Reed, {Elaine F.} and Shaw, {Albert C.} and Hafler, {David A.} and Montgomery, {Ruth R.} and Kleinstein, {Steven H.} and Becker, {Patrice M.} and Augustine, {Alison D.} and Calfee, {Carolyn S.} and Erle, {David J.} and Debakey, {Michael E.} and Corry, {David B.} and Farrah Kheradmand and Atkinson, {Mark A.} and Brakenridge, {Scott C.} and Hough, {Catherine L.} and Messer, {William B.}",

note = "Publisher Copyright: {\textcopyright} 2024, The Author(s).",

year = "2024",

month = dec,

doi = "10.1038/s41467-023-44211-0",

language = "English (US)",

volume = "15",

journal = "Nature communications",

issn = "2041-1723",

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T1 - IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition

AU - IMPACC Data Analysis Group

AU - IMPACC Site Investigators

AU - IMPACC Core Laboratory

AU - IMPACC Clinical Study Team

AU - IMPACC Network

AU - IMPACC Steering Committee

AU - Clinical & Data Coordinating Center (CDCC)

AU - Haslund-Gourley, Benjamin S.

AU - Woloszczuk, Kyra

AU - Hou, Jintong

AU - Connors, Jennifer

AU - Cusimano, Gina

AU - Bell, Mathew

AU - Taramangalam, Bhavani

AU - Fourati, Slim

AU - Mege, Nathan

AU - Bernui, Mariana

AU - Altman, Matthew C.

AU - Krammer, Florian

AU - van Bakel, Harm

AU - Maecker, Holden T.

AU - Rouphael, Nadine

AU - Diray-Arce, Joann

AU - Wigdah, Brian

AU - Kutzler, Michele A.

AU - Cairns, Charles B.

AU - Haddad, Elias K.

AU - Comunale, Mary Ann

AU - Ozonoff, Al

AU - Ehrlich, Lauren I.R.

AU - Melamed, Esther

AU - Sesma, Ana Fernandez

AU - Simon, Viviana

AU - Pulendran, Bali

AU - Nadeau, Kari C.

AU - Davis, Mark M.

AU - McCoey, Grace A.

AU - Sekaly, Rafick

AU - Baden, Lindsey R.

AU - Levy, Ofer

AU - Schaenman, Joanna

AU - Reed, Elaine F.

AU - Shaw, Albert C.

AU - Hafler, David A.

AU - Montgomery, Ruth R.

AU - Kleinstein, Steven H.

AU - Becker, Patrice M.

AU - Augustine, Alison D.

AU - Calfee, Carolyn S.

AU - Erle, David J.

AU - Debakey, Michael E.

AU - Corry, David B.

AU - Kheradmand, Farrah

AU - Atkinson, Mark A.

AU - Brakenridge, Scott C.

AU - Hough, Catherine L.

AU - Messer, William B.

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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U2 - 10.1038/s41467-023-44211-0

DO - 10.1038/s41467-023-44211-0

M3 - Article

C2 - 38195739

AN - SCOPUS:85181877779

SN - 2041-1723

VL - 15

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 404

ER -

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

Abstract

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