IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition. Nature communications 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., van Bakel, H., IMPACC Network, Maecker, H. T., Rouphael, N., Diray-Arce, J., Wigdahl, B., Kutzler, M. A., Cairns, C. B., Haddad, E. K., Comunale, M. A., Ozonoff, A., Ehrlich, L. I., Melamed, E., Sesma, A. F., Simon, V., Pulendran, B., Nadeau, K. C., Davis, M. M., McCoey, G. A., Sekaly, R., Baden, L. R., Levy, O., Schaenman, J., Reed, E. F., Shaw, A. C., Hafler, D. A., Montgomery, R. R., Kleinstein, S. H., Becker, P. M., Augustine, A. D., Calfee, C. S., Erle, D. J., DeBakey, M. E., Corry, D. B., Kheradmand, F., Atkinson, M. A., Brakenridge, S. C., Higuita, N. I., Metcalf, J. P., Hough, C. L., Messer, W. B., Kraft, M., Bime, C., Peters, B., Milliren, C. E., Syphurs, C., McEnaney, K., Barton, B., Lentucci, C., Saluvan, M., Chang, A. C., Hoch, A., Albert, M., Shaheen, T., Kho, A. T., Liu, S., Thomas, S., Chen, J., Murphy, M. D., Cooney, M., Hayati, A. N., Bryant, R., Abraham, J., Jayavelu, N. D., Presnell, S., Jancsyk, T., Maguire, C., Qi, J., Lee, B., Fourati, S., Esserman, D. A., Guan, L., Gygi, J., Pawar, S., Brito, A., Fragiadakis, G. K., Patel, R., Overton, J. A., Vita, R., Westendorf, K., Shannon, C. P., Tebbutt, S. J., Thyagarajan, R. V., Rousseau, J. F., Wylie, D., Triplett, T. A., Kojic, E., Chinthrajah, S., Ahuja, N., Rogers, A. J., Artandi, M., Geng, L., Yendewa, G., Powell, D. L., Kim, J. N., Simmons, B., Goonewardene, I. M., Smith, C. M., Martens, M., Sherman, A. C., Walsh, S. R., Issa, N. C., Salehi-Rad, R., Dela Cruz, C., Farhadian, S., Iwasaki, A., Ko, A. I., Anderson, E. J., Mehta, A. K., Sevransky, J. E., Seyfert-Margolis, V., Leligdowicz, A., Matthay, M. A., Singer, J. P., Kangelaris, K. N., Hendrickson, C. M., Krummel, M. F., Langelier, C. R., Woodruff, P. G., Corry, D. B., Kheradmand, F., Anderson, M. L., Guirgis, F. W., Drevets, D. A., Brown, B. R., Siegel, S. A., Lu, Z., Mosier, J., Kimura, H., Khor, B., van Bakel, H., Rahman, A., Stadlbauer, D., Dutta, J., Xie, H., Kim-Schulze, S., Gonzalez-Reiche, A. S., van de Guchte, A., Carreno, J. M., 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, S. R., Michelotti, G., Wong, K., Jha, M., Viode, A., Kanarek, N., Petrova, B., Zhao, Y., Bosinger, S. E., Boddapati, A. K., Tharp, G. K., Pellegrini, K. L., Beagle, E., Cowan, D., Hamilton, S., Ribeiro, S. P., Hodder, T., Rosen, L. B., Lee, S., Wilson, M. R., Dandekar, R., Alvarenga, B., Rajan, J., Eckalbar, W., Schroeder, A. W., Tsitsiklis, A., Mick, E., Guerrero, Y. S., Love, C., Maliskova, L., Adkisson, M., Siles, N., Geltman, J., Hurley, K., Saksena, M., Altman, D., Srivastava, K., Eaker, L. Q., Bermudez-Gonzalez, M. C., Beach, K. F., Sominsky, L. A., Azad, A. R., Mulder, L. C., Kleiner, G., Lee, A. S., Do, E., Fernandes, A., Manohar, M., Hagan, T., Blish, C. A., Din, H. N., Roque, J., Yang, S., Sigal, N., Chang, I., Tribout, H., Harris, P., Consolo, M., Edwards, C., Lee, E., Lin, E., Croen, B., Semenza, N. C., Rogowski, B., Melnyk, N., Bell, M. R., Furukawa, S., McLin, R., Schearer, P., Sheidy, J., Tegos, G. P., Nagle, C., Smolen, K., Desjardins, M., van Haren, S., Mitre, X., Cauley, J., Li, X., Tong, A., Evans, B., Montesano, C., Licona, J. H., Krauss, J., Chang, J. B., Izaguirre, N., Rooks, R., Elashoff, D., Brook, J., Ramires-Sanchez, E., Llamas, M., Rivera, A., Perdomo, C., Ward, D. C., Magyar, C. E., Fulcher, J. A., Pickering, H. C., Sen, S., Chaudhary, O., Coppi, A., Fournier, J., Mohanty, S., Muenker, C., Nelson, A., Raddassi, K., Rainone, M., Ruff, W. E., Salahuddin, S., Schulz, W. L., Vijayakumar, P., Wang, H., Wunder, E. J., Young, H. P., Rothman, J., Konstorum, A., Chen, E., Cotsapas, C., Grubaugh, N. D., Wang, X., Xu, L., Asashima, H., Bristow, L., Hussaini, L., Hellmeister, K., Samaha, H., Wimalasena, S. T., Cheng, A., Spainhour, C., Scherer, E. M., Johnson, B., Bechnak, A., Ciric, C. R., Hewitt, L., Carter, E., Mcnair, N., Panganiban, B., Huerta, C., Usher, J., Vaysman, T., Holland, S. M., Abe-Jones, Y., Asthana, S., Beagle, A., Bhide, S., Carrillo, S. A., Chak, S., Ghale, R., Gonzalez, A., Jauregui, A., Jones, N., Lea, T., Lee, D., Lota, R., Milush, J., Nguyen, V., Pierce, L., Prasad, P. A., Rao, A., Samad, B., Shaw, C., Sigman, A., Sinha, P., Ward, A., Willmore, A., Zhan, J., Rashid, S., Rodriguez, N., Tang, K., Altamirano, L. T., Betancourt, L., Curiel, C., Sutter, N., Paz, M. T., Tietje-Ulrich, G., Leroux, C., Thakur, N., Vasquez, J. J., Santhosh, L., Song, L., Nelson, E., Moldawer, L. L., Borresen, B., Roth-Manning, B., Ungaro, R. F., Oberhaus, J., Booth, J. L., Sinko, L. A., Brunton, A., Sullivan, P. E., Strnad, M., Lyski, Z. L., Coulter, F. J., Micheleti, C., Conway, M., Francisco, D., Molzahn, A., Erickson, H., Wilson, C. C., Schunk, R., Sierra, B., Hughes, T. 2024; 15 (1): 404
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.
View details for DOI 10.1038/s41467-023-44211-0
View details for PubMedID 38195739
