학술논문
IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition
Document Type
article
Author
Ozonoff, Al; Ehrlich, Lauren IR; Melamed, Esther; Sesma, Ana Fernandez; Simon, Viviana; Pulendran, Bali; Nadeau, Kari C; Davis, Mark M; McCoey, Grace A; Sekaly, Rafick; Baden, Lindsey R; Levy, Ofer; Schaenman, Joanna; Reed, Elaine F; Shaw, Albert C; Hafler, David A; Montgomery, Ruth R; Kleinstein, Steven H; Becker, Patrice M; Augustine, Alison D; Calfee, Carolyn S; Erle, David J; DeBakey, Michael E; Corry, David B; Kheradmand, Farrah; Atkinson, Mark A; Brakenridge, Scott C; Higuita, Nelson I Agudelo; Metcalf, Jordan P; Hough, Catherine L; Messer, William B; Kraft, Monica; Bime, Chris; Peters, Bjoern; Milliren, Carly E; Syphurs, Caitlin; McEnaney, Kerry; Barton, Brenda; Lentucci, Claudia; Saluvan, Mehmet; Chang, Ana C; Hoch, Annmarie; Albert, Marisa; Shaheen, Tanzia; Kho, Alvin T; Liu, Shanshan; Thomas, Sanya; Chen, Jing; Murphy, Maimouna D; Cooney, Mitchell; Hayati, Arash Nemati; Bryant, Robert; Abraham, James; Jayavelu, Naresh Doni; Presnell, Scott; Jancsyk, Tomasz; Maguire, Cole; Qi, Jingjing; Lee, Brian; Fourati, Slim; Esserman, Denise A; Guan, Leying; Gygi, Jeremy; Pawar, Shrikant; Brito, Anderson; Fragiadakis, Gabriela K; Patel, Ravi; Overton, James A; Vita, Randi; Westendorf, Kerstin; Shannon, Casey P; Tebbutt, Scott J; Thyagarajan, Rama V; Rousseau, Justin F; Wylie, Dennis; Triplett, Todd A; Kojic, Erna; Chinthrajah, Sharon; Ahuja, Neera; Rogers, Angela J; Artandi, Maja; Geng, Linda; Yendewa, George; Powell, Debra L; Kim, James N; Simmons, Brent; Goonewardene, I Michael; Smith, Cecilia M; Martens, Mark; Sherman, Amy C; Walsh, Stephen R; Issa, Nicolas C; Salehi-Rad, Ramin; Dela Cruz, Charles; Farhadian, Shelli; Iwasaki, Akiko; Ko, Albert I; Anderson, Evan J; Mehta, Aneesh K; Sevransky, Jonathan E
Source
Nature Communications. 15(1)
Subject
Language
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.