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

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2024年1月9日

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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,
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,
Slim Fourati,
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,
David B. Corry,
Farrah Kheradmand,
Matthew L. Anderson,
Faheem W. Guirgis,
Douglas A. Drevets,
Brent R. Brown,
Sarah A. R. Siegel,
Zhengchun Lu,
Jarrod Mosier,
Hiroki Kimura,
Bernard Khor,
Harm van Bakel,
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,
Deena Altman,
Komal Srivastava,
Lily Q. Eaker,
Maria C. Bermúdez-González,
Katherine F. Beach,
Levy A. Sominsky,
Arman R. Azad,
Lubbertus C. F. Mulder,
Giulio Kleiner,
Alexandra S. Lee,
Evan Do,
Andrea Fernandes,
Monali Manohar,
Thomas Hagan,
Catherine A. Blish,
Hena Naz Din,
Jonasel Roque,
Samuel Yang,
Natalia Sigal,
Iris Chang,
Heather Tribout,
Paul Harris,
Mary Consolo,
Carolyn Edwards,
Edward Lee,
Edward Lin,
Brett Croen,
Nicholas C. Semenza,
Brandon Rogowski,
Nataliya Melnyk,
Mathew R. Bell,
Sara Furukawa,
Renee McLin,
Pamela Schearer,
Julie Sheidy,
George P. Tegos,
Crystal Nagle,
Kinga Smolen,
Michael Desjardins,
Simon van Haren,
Xhoi Mitre,
Jessica Cauley,
Xiaofang Li,
Alexandra Tong,
Bethany Evans,
Christina Montesano,
Jose Humberto Licona,
Jonathan Krauss,
Jun Bai Park Chang,
Natalie Izaguirre,
Rebecca Rooks,
David Elashoff,
Jenny Brook,
Estefania Ramires-Sanchez,
Megan Llamas,
Adreanne Rivera,
Claudia Perdomo,
Dawn C. Ward,
Clara E. Magyar,
Jennifer A. Fulcher,
Harry C. Pickering,
Subha Sen,
Omkar Chaudhary,
Andreas Coppi,
John Fournier,
Subhasis Mohanty,
Catherine Muenker,
Allison Nelson,
Khadir Raddassi,
Michael Rainone,
William E. Ruff,
Syim Salahuddin,
Wade L. Schulz,
Pavithra Vijayakumar,
Haowei Wang,
Elsio Wunder Jr.,
H. Patrick Young,
Jessica Rothman,
Anna Konstorum,
Ernie Chen,
Chris Cotsapas,
Nathan D. Grubaugh,
Xiaomei Wang,
Leqi Xu,
Hiromitsu Asashima,
Laurel Bristow,
Laila Hussaini,
Kieffer Hellmeister,
Hady Samaha,
Sonia Tandon Wimalasena,
Andrew Cheng,
Christine Spainhour,
Erin M. Scherer,
Brandi Johnson,
Amer Bechnak,
Caroline R. Ciric,
Lauren Hewitt,
Erin Carter,
Nina Mcnair,
Bernadine Panganiban,
Christopher Huerta,
Jacob Usher,
Tatyana Vaysman,
Steven M. Holland,
Yumiko Abe-Jones,
Saurabh Asthana,
Alexander Beagle,
Sharvari Bhide,
Sidney A. Carrillo,
Suzanna Chak,
Rajani Ghale,
Ana Gonzalez,
Alejandra Jauregui,
Norman Jones,
Tasha Lea,
Deanna Lee,
Raphael Lota,
Jeff Milush,
Viet Nguyen,
Logan Pierce,
Priya A. Prasad,
Arjun Rao,
Bushra Samad,
Cole Shaw,
Austin Sigman,
Pratik Sinha,
Alyssa Ward,
Andrew Willmore,
Jenny Zhan,
Sadeed Rashid,
Nicklaus Rodriguez,
Kevin Tang,
Luz Torres Altamirano,
Legna Betancourt,
Cindy Curiel,
Nicole Sutter,
Maria Tercero Paz,
Gayelan Tietje-Ulrich,
Carolyn Leroux,
Neeta Thakur,
Joshua J. Vasquez,
Lekshmi Santhosh,
Li-Zhen Song,
Ebony Nelson,
Lyle L. Moldawer,
Brittany Borresen,
Brittney Roth-Manning,
Ricardo F. Ungaro,
Jordan Oberhaus,
J. Leland Booth,
Lauren A. Sinko,
Amanda Brunton,
Peter E. Sullivan,
Matthew Strnad,
Zoe L. Lyski,
Felicity J. Coulter,
Courtney Micheleti,
Michelle Conway,
Dave Francisco,
Allyson Molzahn,
Heidi Erickson,
Connie Cathleen Wilson,
Ron Schunk,
Bianca Sierra,
Trina Hughes,
Holden T. Maecker,
Nadine Rouphael,
Joann Diray-Arce,
Brian Wigdahl,
Michele A. Kutzler,
Charles B. Cairns,
Elias K. Haddad,
Mary Ann Comunale

摘要

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.