TY - JOUR
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 - Kraft, Monica
AU - Bime, Chris
AU - Mosier, Jarrod
AU - Kimura, Hiroki
N1 - Publisher Copyright:
© 2024, The Author(s).
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 -