IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition
Benjamin Haslund-Gourley, Kyra Woloszczuk, Jintong Hou, Jennifer Connors, Gina Cusimano, Matthew R. Bell, Bhavani Taramangalam, Slim Fourati, Nathan Mege, Mariana Bernui, Matthew C. Altman, Florian Krammer, Harm van Bakel, IMPACC Network, Al Ozonoff, Lauren I. R. Ehrlich, Esther Melamed, Ana Fernández-Sesma, Viviana Simon, Bali Pulendran, Kari C. Nadeau, Mark M. Davis, Grace A. McCoey, Rafick‐Pierre Sékaly, 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 Iván 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, Albert Marisa, Tanzia Shaheen, Alvin T. Kho, Shanshan Liu, Sanya Thomas, Jing Chen, Maimouna D. Murphy, Mitchell Cooney, Arash Nemati Hayati, Robert W. Bryant, James Abraham, IMPACC Data Analysis Group, Naresh Doni Jayavelu, Scott Presnell, Tomasz Jancsyk, Cole Maguire, Jingjing Qi, Brian Lee, Slim Fourati, Denise Esserman, Leying Guan, Jeremy P. Gygi, Shrikant Pawar, Anderson F. Brito, Gabriela K. Fragiadakis, Ravi K. Patel, James A. Overton, Randi Vita, Kerstin Westendorf, Casey P. Shannon, Scott J. Tebbutt, IMPACC Site Investigators, Rama Thyagarajan, Justin F. Rousseau, Dennis Wylie, Todd Triplett, Erna Milunka Kojic, R. Sharon Chinthrajah, Neera Ahuja, Angela J. Rogers, Maja Artandi, Linda N. Geng, George A. Yendewa, Debra Powell
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.