tetano
Editor, Senior Moderator
Sci Transl Med
. 2021 Aug 24;eabh2624.
doi: 10.1126/scitranslmed.abh2624. Online ahead of print.
Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19
Monique G P van der Wijst[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Sara E Vazquez[SUP] #[/SUP][SUP] 5 6 7 1 8 [/SUP], George C Hartoularos[SUP] #[/SUP][SUP] 5 3 4 [/SUP], Paul Bastard[SUP] #[/SUP][SUP] 7 9 10 9 11 [/SUP], Tianna Grant[SUP] 5 3 4 [/SUP], Raymund Bueno[SUP] 5 3 4 [/SUP], David S Lee[SUP] 2 3 4 12 [/SUP], John R Greenland[SUP] 2 8 5 [/SUP], Yang Sun[SUP] 2 3 4 12 [/SUP], Richard Perez[SUP] 2 3 13 [/SUP], Anton Ogorodnikov[SUP] 2 3 4 [/SUP], Alyssa Ward[SUP] 3 4 [/SUP], Sabrina A Mann[SUP] 5 8 14 [/SUP], Kara L Lynch[SUP] 5 15 16 [/SUP], Cassandra Yun[SUP] 15 16 [/SUP], Diane V Havlir[SUP] 17 [/SUP], Gabriel Chamie[SUP] 17 [/SUP], Carina Marquez[SUP] 5 17 [/SUP], Bryan Greenhouse[SUP] 17 [/SUP], Michail S Lionakis[SUP] 18 [/SUP], Philip J Norris[SUP] 3 15 16 19 [/SUP], Larry J Dumont[SUP] 3 10 20 21 22 [/SUP], Kathleen Kelly[SUP] 3 20 [/SUP], Peng Zhang[SUP] 7 11 [/SUP], Qian Zhang[SUP] 7 11 [/SUP], Adrian Gervais[SUP] 9 9 11 [/SUP], Tom Le Voyer[SUP] 9 11 [/SUP], Alexander Whatley[SUP] 23 [/SUP], Yichen Si[SUP] 12 24 [/SUP], Ashley Byrne[SUP] 14 [/SUP], Alexis J Combes[SUP] 2 12 25 26 [/SUP], Arjun Arkal Rao[SUP] 5 12 25 26 [/SUP], Yun S Song[SUP] 11 14 23 27 [/SUP], Gabriela K Fragiadakis[SUP] 2 4 12 26 [/SUP], Kirsten Kangelaris[SUP] 2 28 [/SUP], Carolyn S Calfee[SUP] 29 [/SUP], David J Erle[SUP] 5 3 12 15 [/SUP], Carolyn Hendrickson[SUP] 29 [/SUP], Matthew F Krummel[SUP] 2 12 25 [/SUP], Prescott G Woodruff[SUP] 12 29 [/SUP], Charles R Langelier[SUP] 30 [/SUP], Jean-Laurent Casanova[SUP] #[/SUP][SUP] 31 9 11 32 [/SUP], Joseph L Derisi[SUP] #[/SUP][SUP] 33 4 8 14 [/SUP], Mark S Anderson[SUP] #[/SUP][SUP] 34 1 35 [/SUP], Chun Jimmie Ye[SUP] #[/SUP][SUP] 36 4 12 14 37 38 39 [/SUP], UCSF COMET consortium
Collaborators, Affiliations
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.
. 2021 Aug 24;eabh2624.
doi: 10.1126/scitranslmed.abh2624. Online ahead of print.
Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19
Monique G P van der Wijst[SUP] #[/SUP][SUP] 1 2 3 4 [/SUP], Sara E Vazquez[SUP] #[/SUP][SUP] 5 6 7 1 8 [/SUP], George C Hartoularos[SUP] #[/SUP][SUP] 5 3 4 [/SUP], Paul Bastard[SUP] #[/SUP][SUP] 7 9 10 9 11 [/SUP], Tianna Grant[SUP] 5 3 4 [/SUP], Raymund Bueno[SUP] 5 3 4 [/SUP], David S Lee[SUP] 2 3 4 12 [/SUP], John R Greenland[SUP] 2 8 5 [/SUP], Yang Sun[SUP] 2 3 4 12 [/SUP], Richard Perez[SUP] 2 3 13 [/SUP], Anton Ogorodnikov[SUP] 2 3 4 [/SUP], Alyssa Ward[SUP] 3 4 [/SUP], Sabrina A Mann[SUP] 5 8 14 [/SUP], Kara L Lynch[SUP] 5 15 16 [/SUP], Cassandra Yun[SUP] 15 16 [/SUP], Diane V Havlir[SUP] 17 [/SUP], Gabriel Chamie[SUP] 17 [/SUP], Carina Marquez[SUP] 5 17 [/SUP], Bryan Greenhouse[SUP] 17 [/SUP], Michail S Lionakis[SUP] 18 [/SUP], Philip J Norris[SUP] 3 15 16 19 [/SUP], Larry J Dumont[SUP] 3 10 20 21 22 [/SUP], Kathleen Kelly[SUP] 3 20 [/SUP], Peng Zhang[SUP] 7 11 [/SUP], Qian Zhang[SUP] 7 11 [/SUP], Adrian Gervais[SUP] 9 9 11 [/SUP], Tom Le Voyer[SUP] 9 11 [/SUP], Alexander Whatley[SUP] 23 [/SUP], Yichen Si[SUP] 12 24 [/SUP], Ashley Byrne[SUP] 14 [/SUP], Alexis J Combes[SUP] 2 12 25 26 [/SUP], Arjun Arkal Rao[SUP] 5 12 25 26 [/SUP], Yun S Song[SUP] 11 14 23 27 [/SUP], Gabriela K Fragiadakis[SUP] 2 4 12 26 [/SUP], Kirsten Kangelaris[SUP] 2 28 [/SUP], Carolyn S Calfee[SUP] 29 [/SUP], David J Erle[SUP] 5 3 12 15 [/SUP], Carolyn Hendrickson[SUP] 29 [/SUP], Matthew F Krummel[SUP] 2 12 25 [/SUP], Prescott G Woodruff[SUP] 12 29 [/SUP], Charles R Langelier[SUP] 30 [/SUP], Jean-Laurent Casanova[SUP] #[/SUP][SUP] 31 9 11 32 [/SUP], Joseph L Derisi[SUP] #[/SUP][SUP] 33 4 8 14 [/SUP], Mark S Anderson[SUP] #[/SUP][SUP] 34 1 35 [/SUP], Chun Jimmie Ye[SUP] #[/SUP][SUP] 36 4 12 14 37 38 39 [/SUP], UCSF COMET consortium
Collaborators, Affiliations
- PMID: 34429372
- DOI: 10.1126/scitranslmed.abh2624
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.