Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19
Monique G. P. van der Wijst, Sara E. Vazquez, George C. Hartoularos, Paul Bastard, Tianna Grant, Raymund Bueno, David S. Lee, John R. Greenland, Yang Sun, Richard Perez, Anton Ogorodnikov, Alyssa Ward, Sabrina A. Mann, Kara L. Lynch, Cassandra Yun, Diane V. Havlir, Gabriel Chamie, Carina Marquez, Bryan Greenhouse, Michail S. Lionakis, Philip J. Norris, Larry J. Dumont, Kathleen Kelly, Peng Zhang, Qian Zhang, Adrian Gervais, Tom Le Voyer, Alexander Whatley, Yichen Si, Ashley Byrne, Alexis J. Combes, Arjun Arkal Rao, Yun S. Song, Gabriela K. Fragiadakis, Kirsten Kangelaris, Carolyn S. Calfee, David J. Erle, Carolyn Hendrickson, Matthew F. Krummel, Prescott G. Woodruff, Charles R. Langelier, Jean-Laurent Casanova, Joseph L. DeRisi, Mark S. Anderson, Chun Jimmie Ye, and on behalf of the UCSF COMET Consortium
Abstract
Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.
Datasets
1. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19
Metadata
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BEST.GUESS
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Source data
https://cellxgene.cziscience.com/collections/7d7cabfd-1d1f-40af-96b7-26a0825a306d
Alias names
GSE168453, PMID34429372, PMC8601717
Cite this study
van der Wijst, M.G., Vazquez, S.E., Hartoularos, G.C., Bastard, P., Grant, T., Bueno, R., Lee, D.S., Greenland, J.R., Sun, Y., Perez, R. and Ogorodnikov, A., 2021. Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19. Science translational medicine, 13(612), p.eabh2624. https://doi.org/10.1126/scitranslmed.abh2624
