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); 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; Holden T. Maecker; Nadine Rouphael; Joann Diray-Arce; Brian Wigdah; Michele A. Kutzler; Charles B. Cairns; Elias K. Haddad; Mary Ann Comunale; Al Ozonoff; Lauren I.R. Ehrlich; Esther Melamed; Ana Fernandez Sesma; Viviana Simon; Bali Pulendran; Kari C. Nadeau; Mark M. Davis; Grace A. McCoey; Rafick Sekaly; Lindsey R. Baden; Ofer Levy; Joanna Schaenman; Elaine F. Reed; Albert C. Shaw; David A. Hafler; Ruth R. Montgomery; Steven H. Kleinstein; Patrice M. Becker; Alison D. Augustine; Carolyn S. Calfee; David J. Erle; Michael E. Debakey; David B. Corry; Farrah Kheradmand; Mark A. Atkinson; Scott C. Brakenridge; Nelson I. Agudelo Higuita; Jordan P. Metcalf; Catherine L. Hough; William B. Messer; Monica Kraft; Chris Bime; Bjoern Peters; Carly E. Milliren; Caitlin Syphurs; Kerry McEnaney; Brenda Barton; Claudia Lentucci; Mehmet Saluvan; Ana C. Chang; Annmarie Hoch; Marisa Albert; Tanzia Shaheen; Alvin T. Kho; Shanshan Liu; Sanya Thomas; Jing Chen; Maimouna D. Murphy; Mitchell Cooney; Arash Nemati Hayati; Robert Bryant; James Abraham; Naresh Doni Jayavelu; Scott Presnell; Tomasz Jancsyk; Cole Maguire; Jingjing Qi; Brian Lee; Denise A. Esserman; Leying Guan; Jeremy Gygi; Shrikant Pawar; Anderson Brito; Gabriela K. Fragiadakis; Ravi Patel; James A. Overton; Randi Vita; Kerstin Westendorf; Casey P. Shannon; Scott J. Tebbutt; Rama V. Thyagarajan; Justin F. Rousseau; Dennis Wylie; Todd A. Triplett; Erna Kojic; Sharon Chinthrajah; Neera Ahuja; Angela J. Rogers; Maja Artandi; Linda Geng; George Yendewa; Debra L. Powell; James N. Kim; Brent Simmons; I. Michael Goonewardene; Cecilia M. Smith; Mark Martens; Amy C. Sherman; Stephen R. Walsh; Nicolas C. Issa; Ramin Salehi-Rad; Charles Dela Cruz; Shelli Farhadian; Akiko Iwasaki; Albert I. Ko; Evan J. Anderson; Aneesh K. Mehta; Jonathan E. Sevransky; Vicki Seyfert-Margolis; Aleksandra Leligdowicz; Michael A. Matthay; Jonathan P. Singer; Kirsten N. Kangelaris; Carolyn M. Hendrickson; Matthew F. Krummel; Charles R. Langelier; Prescott G. Woodruff; Matthew L. Anderson; Faheem W. Guirgis; Douglas A. Drevets; Brent R. Brown; Sarah A.R. Siegel; Zhengchun Lu; Jarrod Mosier; Hiroki Kimura; Bernard Khor; Adeeb Rahman; Daniel Stadlbauer; Jayeeta Dutta; Hui Xie; Seunghee Kim-Schulze; Ana Silvia Gonzalez-Reiche; Adriana van de Guchte; Juan Manuel Carreño; Gagandeep Singh; Ariel Raskin; Johnstone Tcheou; Dominika Bielak; Hisaaki Kawabata; Geoffrey Kelly; Manishkumar Patel; Kai Nie; Temima Yellin; Miriam Fried; Leeba Sullivan; Sara Morris; Scott Sieg; Hanno Steen; Patrick van Zalm; Benoit Fatou; Kevin Mendez; Jessica Lasky-Su; Scott R. Hutton; Greg Michelotti; Kari Wong; Meenakshi Jha; Arthur Viode; Naama Kanarek; Boryana Petrova; Yujiao Zhao; Steven E. Bosinger; Arun K. Boddapati; Greg K. Tharp; Kathryn L. Pellegrini; Elizabeth Beagle; David Cowan; Sydney Hamilton; Susan Pereira Ribeiro; Thomas Hodder; Lindsey B. Rosen; Serena Lee; Michael R. Wilson; Ravi Dandekar; Bonny Alvarenga; Jayant Rajan; Walter Eckalbar; Andrew W. Schroeder; Alexandra Tsitsiklis; Eran Mick; Yanedth Sanchez Guerrero; Christina Love; Lenka Maliskova; Michael Adkisson; Nadia Siles; Janelle Geltman; Kerin Hurley; Miti Saksena; Pratik Sinha

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), 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 BakelHolden T. Maecker, Nadine Rouphael, Joann Diray-Arce, Brian Wigdah, Michele A. Kutzler, Charles B. Cairns, Elias K. Haddad, Mary Ann Comunale, Al Ozonoff, Lauren I.R. Ehrlich, Esther Melamed, Ana Fernandez Sesma, Viviana Simon, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Grace A. McCoey, Rafick Sekaly, Lindsey R. Baden, Ofer Levy, Joanna Schaenman, Elaine F. Reed, Albert C. Shaw, David A. Hafler, Ruth R. Montgomery, Steven H. Kleinstein, Patrice M. Becker, Alison D. Augustine, Carolyn S. Calfee, David J. Erle, Michael E. Debakey, David B. Corry, Farrah Kheradmand, Mark A. Atkinson, Scott C. Brakenridge, Nelson I. Agudelo Higuita, Jordan P. Metcalf, Catherine L. Hough, William B. Messer, Monica Kraft, Chris Bime, Bjoern Peters, Carly E. Milliren, Caitlin Syphurs, Kerry McEnaney, Brenda Barton, Claudia Lentucci, Mehmet Saluvan, Ana C. Chang, Annmarie Hoch, Marisa Albert, Tanzia Shaheen, Alvin T. Kho, Shanshan Liu, Sanya Thomas, Jing Chen, Maimouna D. Murphy, Mitchell Cooney, Arash Nemati Hayati, Robert Bryant, James Abraham, Naresh Doni Jayavelu, Scott Presnell, Tomasz Jancsyk, Cole Maguire, Jingjing Qi, Brian Lee, Denise A. Esserman, Leying Guan, Jeremy Gygi, Shrikant Pawar, Anderson Brito, Gabriela K. Fragiadakis, Ravi Patel, James A. Overton, Randi Vita, Kerstin Westendorf, Casey P. Shannon, Scott J. Tebbutt, Rama V. Thyagarajan, Justin F. Rousseau, Dennis Wylie, Todd A. Triplett, Erna Kojic, Sharon Chinthrajah, Neera Ahuja, Angela J. Rogers, Maja Artandi, Linda Geng, George Yendewa, Debra L. Powell, James N. Kim, Brent Simmons, I. Michael Goonewardene, Cecilia M. Smith, Mark Martens, Amy C. Sherman, Stephen R. Walsh, Nicolas C. Issa, Ramin Salehi-Rad, Charles Dela Cruz, Shelli Farhadian, Akiko Iwasaki, Albert I. Ko, Evan J. Anderson, Aneesh K. Mehta, Jonathan E. Sevransky, Vicki Seyfert-Margolis, Aleksandra Leligdowicz, Michael A. Matthay, Jonathan P. Singer, Kirsten N. Kangelaris, Carolyn M. Hendrickson, Matthew F. Krummel, Charles R. Langelier, Prescott G. Woodruff, Matthew L. Anderson, Faheem W. Guirgis, Douglas A. Drevets, Brent R. Brown, Sarah A.R. Siegel, Zhengchun Lu, Jarrod Mosier, Hiroki Kimura, Bernard Khor, Adeeb Rahman, Daniel Stadlbauer, Jayeeta Dutta, Hui Xie, Seunghee Kim-Schulze, Ana Silvia Gonzalez-Reiche, Adriana van de Guchte, Juan Manuel Carreño, Gagandeep Singh, Ariel Raskin, Johnstone Tcheou, Dominika Bielak, Hisaaki Kawabata, Geoffrey Kelly, Manishkumar Patel, Kai Nie, Temima Yellin, Miriam Fried, Leeba Sullivan, Sara Morris, Scott Sieg, Hanno Steen, Patrick van Zalm, Benoit Fatou, Kevin Mendez, Jessica Lasky-Su, Scott R. Hutton, Greg Michelotti, Kari Wong, Meenakshi Jha, Arthur Viode, Naama Kanarek, Boryana Petrova, Yujiao Zhao, Steven E. Bosinger, Arun K. Boddapati, Greg K. Tharp, Kathryn L. Pellegrini, Elizabeth Beagle, David Cowan, Sydney Hamilton, Susan Pereira Ribeiro, Thomas Hodder, Lindsey B. Rosen, Serena Lee, Michael R. Wilson, Ravi Dandekar, Bonny Alvarenga, Jayant Rajan, Walter Eckalbar, Andrew W. Schroeder, Alexandra Tsitsiklis, Eran Mick, Yanedth Sanchez Guerrero, Christina Love, Lenka Maliskova, Michael Adkisson, Nadia Siles, Janelle Geltman, Kerin Hurley, Miti Saksena, Pratik Sinha

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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
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

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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), Haslund-Gourley, B. S., Woloszczuk, K., Hou, J., Connors, J., Cusimano, G., Bell, M., Taramangalam, B., Fourati, S., Mege, N., Bernui, M., Altman, M. C., Krammer, F., ... Sinha, P. (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

@article{86ff409d94b94133a02aaa2ecb629437,

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 {Agudelo Higuita}, {Nelson I.} and Metcalf, {Jordan P.} and Hough, {Catherine L.} and Messer, {William B.} and Monica Kraft and Chris Bime and Bjoern Peters and Milliren, {Carly E.} and Caitlin Syphurs and Kerry McEnaney and Brenda Barton and Claudia Lentucci and Mehmet Saluvan and Chang, {Ana C.} and Annmarie Hoch and Marisa Albert and Tanzia Shaheen and Kho, {Alvin T.} and Shanshan Liu and Sanya Thomas and Jing Chen and Murphy, {Maimouna D.} and Mitchell Cooney and Hayati, {Arash Nemati} and Robert Bryant and James Abraham and Jayavelu, {Naresh Doni} and Scott Presnell and Tomasz Jancsyk and Cole Maguire and Jingjing Qi and Brian Lee and Esserman, {Denise A.} and Leying Guan and Jeremy Gygi and Shrikant Pawar and Anderson Brito and Fragiadakis, {Gabriela K.} and Ravi Patel and Overton, {James A.} and Randi Vita and Kerstin Westendorf and Shannon, {Casey P.} and Tebbutt, {Scott J.} and Thyagarajan, {Rama V.} and Rousseau, {Justin F.} and Dennis Wylie and Triplett, {Todd A.} and Erna Kojic and Sharon Chinthrajah and Neera Ahuja and Rogers, {Angela J.} and Maja Artandi and Linda Geng and George Yendewa and Powell, {Debra L.} and Kim, {James N.} and Brent Simmons and Goonewardene, {I. Michael} and Smith, {Cecilia M.} and Mark Martens and Sherman, {Amy C.} and Walsh, {Stephen R.} and Issa, {Nicolas C.} and Ramin Salehi-Rad and {Dela Cruz}, Charles and Shelli Farhadian and Akiko Iwasaki and Ko, {Albert I.} and Anderson, {Evan J.} and Mehta, {Aneesh K.} and Sevransky, {Jonathan E.} and Vicki Seyfert-Margolis and Aleksandra Leligdowicz and Matthay, {Michael A.} and Singer, {Jonathan P.} and Kangelaris, {Kirsten N.} and Hendrickson, {Carolyn M.} and Krummel, {Matthew F.} and Langelier, {Charles R.} and Woodruff, {Prescott G.} and Anderson, {Matthew L.} and Guirgis, {Faheem W.} and Drevets, {Douglas A.} and Brown, {Brent R.} and Siegel, {Sarah A.R.} and Zhengchun Lu and Jarrod Mosier and Hiroki Kimura and Bernard Khor and Adeeb Rahman and Daniel Stadlbauer and Jayeeta Dutta and Hui Xie and Seunghee Kim-Schulze and Gonzalez-Reiche, {Ana Silvia} and {van de Guchte}, Adriana and Carre{\~n}o, {Juan Manuel} and Gagandeep Singh and Ariel Raskin and Johnstone Tcheou and Dominika Bielak and Hisaaki Kawabata and Geoffrey Kelly and Manishkumar Patel and Kai Nie and Temima Yellin and Miriam Fried and Leeba Sullivan and Sara Morris and Scott Sieg and Hanno Steen and {van Zalm}, Patrick and Benoit Fatou and Kevin Mendez and Jessica Lasky-Su and Hutton, {Scott R.} and Greg Michelotti and Kari Wong and Meenakshi Jha and Arthur Viode and Naama Kanarek and Boryana Petrova and Yujiao Zhao and Bosinger, {Steven E.} and Boddapati, {Arun K.} and Tharp, {Greg K.} and Pellegrini, {Kathryn L.} and Elizabeth Beagle and David Cowan and Sydney Hamilton and Ribeiro, {Susan Pereira} and Thomas Hodder and Rosen, {Lindsey B.} and Serena Lee and Wilson, {Michael R.} and Ravi Dandekar and Bonny Alvarenga and Jayant Rajan and Walter Eckalbar and Schroeder, {Andrew W.} and Alexandra Tsitsiklis and Eran Mick and Guerrero, {Yanedth Sanchez} and Christina Love and Lenka Maliskova and Michael Adkisson and Nadia Siles and Janelle Geltman and Kerin Hurley and Miti Saksena and Pratik Sinha",

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

year = "2024",

month = dec,

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

language = "English",

volume = "15",

journal = "Nature communications",

issn = "2041-1723",

number = "1",

}

IMPACC Data Analysis Group, IMPACC Site Investigators, IMPACC Core Laboratory, IMPACC Clinical Study Team, IMPACC Network, IMPACC Steering Committee, Clinical & Data Coordinating Center (CDCC), Haslund-Gourley, BS, Woloszczuk, K, Hou, J, Connors, J, Cusimano, G, Bell, M, Taramangalam, B, Fourati, S, Mege, N, Bernui, M, Altman, MC, Krammer, F, van Bakel, H, Maecker, HT, Rouphael, N, Diray-Arce, J, Wigdah, B, Kutzler, MA, Cairns, CB, Haddad, EK, Comunale, MA, Ozonoff, A, Ehrlich, LIR, Melamed, E, Sesma, AF, Simon, V, Pulendran, B, Nadeau, KC, Davis, MM, McCoey, GA, Sekaly, R, Baden, LR, Levy, O, Schaenman, J, Reed, EF, Shaw, AC, Hafler, DA, Montgomery, RR, Kleinstein, SH, Becker, PM, Augustine, AD, Calfee, CS, Erle, DJ, Debakey, ME, Corry, DB, Kheradmand, F, Atkinson, MA, Brakenridge, SC, Agudelo Higuita, NI, Metcalf, JP, Hough, CL, Messer, WB, Kraft, M, Bime, C, Peters, B, Milliren, CE, Syphurs, C, McEnaney, K, Barton, B, Lentucci, C, Saluvan, M, Chang, AC, Hoch, A, Albert, M, Shaheen, T, Kho, AT, Liu, S, Thomas, S, Chen, J, Murphy, MD, Cooney, M, Hayati, AN, Bryant, R, Abraham, J, Jayavelu, ND, Presnell, S, Jancsyk, T, Maguire, C, Qi, J, Lee, B, Esserman, DA, Guan, L, Gygi, J, Pawar, S, Brito, A, Fragiadakis, GK, Patel, R, Overton, JA, Vita, R, Westendorf, K, Shannon, CP, Tebbutt, SJ, Thyagarajan, RV, Rousseau, JF, Wylie, D, Triplett, TA, Kojic, E, Chinthrajah, S, Ahuja, N, Rogers, AJ, Artandi, M, Geng, L, Yendewa, G, Powell, DL, Kim, JN, Simmons, B, Goonewardene, IM, Smith, CM, Martens, M, Sherman, AC, Walsh, SR, Issa, NC, Salehi-Rad, R, Dela Cruz, C, Farhadian, S, Iwasaki, A, Ko, AI, Anderson, EJ, Mehta, AK, Sevransky, JE, Seyfert-Margolis, V, Leligdowicz, A, Matthay, MA, Singer, JP, Kangelaris, KN, Hendrickson, CM, Krummel, MF, Langelier, CR, Woodruff, PG, Anderson, ML, Guirgis, FW, Drevets, DA, Brown, BR, Siegel, SAR, Lu, Z, Mosier, J, Kimura, H, Khor, B, Rahman, A, Stadlbauer, D, Dutta, J, Xie, H, Kim-Schulze, S, Gonzalez-Reiche, AS, van de Guchte, A, Carreño, JM, Singh, G, Raskin, A, Tcheou, J, Bielak, D, Kawabata, H, Kelly, G, Patel, M, Nie, K, Yellin, T, Fried, M, Sullivan, L, Morris, S, Sieg, S, Steen, H, van Zalm, P, Fatou, B, Mendez, K, Lasky-Su, J, Hutton, SR, Michelotti, G, Wong, K, Jha, M, Viode, A, Kanarek, N, Petrova, B, Zhao, Y, Bosinger, SE, Boddapati, AK, Tharp, GK, Pellegrini, KL, Beagle, E, Cowan, D, Hamilton, S, Ribeiro, SP, Hodder, T, Rosen, LB, Lee, S, Wilson, MR, Dandekar, R, Alvarenga, B, Rajan, J, Eckalbar, W, Schroeder, AW, Tsitsiklis, A, Mick, E, Guerrero, YS, Love, C, Maliskova, L, Adkisson, M, Siles, N, Geltman, J, Hurley, K, Saksena, M & Sinha, P 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

TY - JOUR

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

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AU - IMPACC Site Investigators

AU - IMPACC Core Laboratory

AU - IMPACC Clinical Study Team

AU - IMPACC Network

AU - IMPACC Steering Committee

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AU - Hou, Jintong

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AU - Cusimano, Gina

AU - Bell, Mathew

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AU - Maecker, Holden T.

AU - Rouphael, Nadine

AU - Diray-Arce, Joann

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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

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AU - Reed, Elaine F.

AU - Shaw, Albert C.

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AU - Becker, Patrice M.

AU - Augustine, Alison D.

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AU - Debakey, Michael E.

AU - Corry, David B.

AU - Kheradmand, Farrah

AU - Atkinson, Mark A.

AU - Brakenridge, Scott C.

AU - Agudelo Higuita, Nelson I.

AU - Metcalf, Jordan P.

AU - Hough, Catherine L.

AU - Messer, William B.

AU - Kraft, Monica

AU - Bime, Chris

AU - Peters, Bjoern

AU - Milliren, Carly E.

AU - Syphurs, Caitlin

AU - McEnaney, Kerry

AU - Barton, Brenda

AU - Lentucci, Claudia

AU - Saluvan, Mehmet

AU - Chang, Ana C.

AU - Hoch, Annmarie

AU - Albert, Marisa

AU - Shaheen, Tanzia

AU - Kho, Alvin T.

AU - Liu, Shanshan

AU - Thomas, Sanya

AU - Chen, Jing

AU - Murphy, Maimouna D.

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AU - Hayati, Arash Nemati

AU - Bryant, Robert

AU - Abraham, James

AU - Jayavelu, Naresh Doni

AU - Presnell, Scott

AU - Jancsyk, Tomasz

AU - Maguire, Cole

AU - Qi, Jingjing

AU - Lee, Brian

AU - Esserman, Denise A.

AU - Guan, Leying

AU - Gygi, Jeremy

AU - Pawar, Shrikant

AU - Brito, Anderson

AU - Fragiadakis, Gabriela K.

AU - Patel, Ravi

AU - Overton, James A.

AU - Vita, Randi

AU - Westendorf, Kerstin

AU - Shannon, Casey P.

AU - Tebbutt, Scott J.

AU - Thyagarajan, Rama V.

AU - Rousseau, Justin F.

AU - Wylie, Dennis

AU - Triplett, Todd A.

AU - Kojic, Erna

AU - Chinthrajah, Sharon

AU - Ahuja, Neera

AU - Rogers, Angela J.

AU - Artandi, Maja

AU - Geng, Linda

AU - Yendewa, George

AU - Powell, Debra L.

AU - Kim, James N.

AU - Simmons, Brent

AU - Goonewardene, I. Michael

AU - Smith, Cecilia M.

AU - Martens, Mark

AU - Sherman, Amy C.

AU - Walsh, Stephen R.

AU - Issa, Nicolas C.

AU - Salehi-Rad, Ramin

AU - Dela Cruz, Charles

AU - Farhadian, Shelli

AU - Iwasaki, Akiko

AU - Ko, Albert I.

AU - Anderson, Evan J.

AU - Mehta, Aneesh K.

AU - Sevransky, Jonathan E.

AU - Seyfert-Margolis, Vicki

AU - Leligdowicz, Aleksandra

AU - Matthay, Michael A.

AU - Singer, Jonathan P.

AU - Kangelaris, Kirsten N.

AU - Hendrickson, Carolyn M.

AU - Krummel, Matthew F.

AU - Langelier, Charles R.

AU - Woodruff, Prescott G.

AU - Anderson, Matthew L.

AU - Guirgis, Faheem W.

AU - Drevets, Douglas A.

AU - Brown, Brent R.

AU - Siegel, Sarah A.R.

AU - Lu, Zhengchun

AU - Mosier, Jarrod

AU - Kimura, Hiroki

AU - Khor, Bernard

AU - Rahman, Adeeb

AU - Stadlbauer, Daniel

AU - Dutta, Jayeeta

AU - Xie, Hui

AU - Kim-Schulze, Seunghee

AU - Gonzalez-Reiche, Ana Silvia

AU - van de Guchte, Adriana

AU - Carreño, Juan Manuel

AU - Singh, Gagandeep

AU - Raskin, Ariel

AU - Tcheou, Johnstone

AU - Bielak, Dominika

AU - Kawabata, Hisaaki

AU - Kelly, Geoffrey

AU - Patel, Manishkumar

AU - Nie, Kai

AU - Yellin, Temima

AU - Fried, Miriam

AU - Sullivan, Leeba

AU - Morris, Sara

AU - Sieg, Scott

AU - Steen, Hanno

AU - van Zalm, Patrick

AU - Fatou, Benoit

AU - Mendez, Kevin

AU - Lasky-Su, Jessica

AU - Hutton, Scott R.

AU - Michelotti, Greg

AU - Wong, Kari

AU - Jha, Meenakshi

AU - Viode, Arthur

AU - Kanarek, Naama

AU - Petrova, Boryana

AU - Zhao, Yujiao

AU - Bosinger, Steven E.

AU - Boddapati, Arun K.

AU - Tharp, Greg K.

AU - Pellegrini, Kathryn L.

AU - Beagle, Elizabeth

AU - Cowan, David

AU - Hamilton, Sydney

AU - Ribeiro, Susan Pereira

AU - Hodder, Thomas

AU - Rosen, Lindsey B.

AU - Lee, Serena

AU - Wilson, Michael R.

AU - Dandekar, Ravi

AU - Alvarenga, Bonny

AU - Rajan, Jayant

AU - Eckalbar, Walter

AU - Schroeder, Andrew W.

AU - Tsitsiklis, Alexandra

AU - Mick, Eran

AU - Guerrero, Yanedth Sanchez

AU - Love, Christina

AU - Maliskova, Lenka

AU - Adkisson, Michael

AU - Siles, Nadia

AU - Geltman, Janelle

AU - Hurley, Kerin

AU - Saksena, Miti

AU - Sinha, Pratik

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.

UR - http://www.scopus.com/inward/record.url?scp=85181877779&partnerID=8YFLogxK

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

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