Single-cell epitope and RNA-sequencing reveals the systemic immune associations with type I interferon autoantibodies in COVID-19

Autor: van der Wijst, Monique G.P., Vazquez, Sara E., Hartoularos, George C., Bastard, Paul, Grant, Tianna, Bueno, Raymund, Lee, David S., Greenland, John R., Sun, Yang, Perez, Richard, Ogorodnikov, Anton, Ward, Alyssa, Mann, Sabrina A., Lynch, Kara L., Yun, Cassandra, Havlir, Diane V., Chamie, Gabriel, Marquez, Carina, Greenhouse, Bryan, Lionakis, Michail S., Norris, Philip J., Dumont, Larry J., Kelly, Kathleen, Zhang, Peng, Zhang, Qian, Gervais, Adrian, Le Voyer, Tom, Whatley, Alexander, Si, Yichen, Byrne, Ashley, Combes, Alexis J., Rao, Arjun Arkal, Song, Yun S., Fragiadakis, Gabriela K., Kangelaris, Kirsten, Calfee, Carolyn S., Erle, David J., Hendrickson, Carolyn, Krummel, Matthew F., Woodruff, Prescott G., Langelier, Charles R., Casanova, Jean-Laurent, Derisi, Joseph L., Anderson, Mark S., Ye, Chun Jimmie
Jazyk: angličtina
Rok vydání: 2021
Předmět:
DOI: 10.5281/zenodo.5148861
Popis: 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 cases and 6% of patients with severe cases. We found no type I IFN autoantibodies in individuals with moderate cases. 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 cases. This was especially evident in dendritic cell populations isolated from critical cases producing type I IFN-specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) on the surface of monocytes isolated from patients with critical cases early in the disease course. LAIR-1 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.
Type I interferon autoantibodies in COVID-19 are associated with deficient interferon response and elevated LAIR-1 expression in peripheral leukocytes.
Databáze: OpenAIRE
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