| Title: |
Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19 |
| Authors: |
van der Wijst, Monique GP; 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; consortium, on behalf of the UCSF COMET; Abe-Jones, Yumiko; Alvarenga, Bonny; Asthana, Saurabh; Beagle, Alexander; Bhakta, Tanvi; Bhide, Sharvari; Cai, Cathy; Calvo, Maria; Carrillo, Sidney A; Chak, Suzanna; Collins, Zachary; Dandekar, Ravi; Darmanis, Spyros; Esmaili, Armond; Ghale, Rajani; Giberson, Jeremy; Glenn, Pat; Gonzalez, Ana; Jauregui, Alejandra; Jones, Norman; Ke, Serena; Lea, Tasha; Lee, Deanna; Lelidowicz, Aleskandra; Liu, Kathleen; Lota, Raphael; Matthay, Michael; Milush, Jeff; Nguyen, Viet; Nigam, Nishita; Ortiz, Gabe; Pierce, Logan; Prasad, Priya; Rajan, Jayant; Rashid, Ahmad Sadeed; Rodriguez, Nicklaus; Samad, Bushra; Scarlet, Diane; Shaw, Cole; Sigman, Austin; Sinha, Pratik; Spitzer, Matthew; Tang, Kevin; Altamirano, Luz Torres; Tumurbaatar, Erden; Willmore, Andrew; Wilson, Michael; Withers, Reese; Yee, Kimberly; Zamecnik, Colin; Zhan, Jenny; Zhou, Mingyue |
| Source: |
Science Translational Medicine, vol 13, iss 612 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2021 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3204 Immunology (for-2020); Autoimmune Disease (rcdc); Clinical Research (rcdc); Coronaviruses (rcdc); Infectious Diseases (rcdc); Emerging Infectious Diseases (rcdc); Genetics (rcdc); Biodefense (rcdc); Lung (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); Inflammatory and immune system (hrcs-hc); 3 Good Health and Well Being (sdg); Autoantibodies (mesh); COVID-19 (mesh); Humans (mesh); Interferon Type I (mesh); UCSF COMET consortium; 06 Biological Sciences (for); 11 Medical and Health Sciences (for); 3206 Medical biotechnology (for-2020); 4003 Biomedical engineering (for-2020) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt0s86572x; https://escholarship.org/uc/item/0s86572x; https://escholarship.org/content/qt0s86572x/qt0s86572x.pdf |
| DOI: |
10.1126/scitranslmed.abh2624 |
| Availability: |
https://escholarship.org/uc/item/0s86572x; https://escholarship.org/content/qt0s86572x/qt0s86572x.pdf; https://doi.org/10.1126/scitranslmed.abh2624 |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.E98C6137 |
| Database: |
BASE |