Details

Autor(en) / Beteiligte

• 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

Titel

Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19

Ist Teil von

• Science translational medicine, 2021-09, Vol.13 (612), p.eabh2624

Ort / Verlag

United States

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.