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Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19: Anti-IFN antibodies in critical COVID-19 correlate with poor ISG response and upregulation of LAIR1 surface protein in PBMCs.
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.
Affiliation
  • van der Wijst MGP; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • Vazquez SE; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Hartoularos GC; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
  • Bastard P; Medical Scientist Training Program, University of California. San Francisco, CA, USA.
  • Grant T; Tetrad Graduate Program, University of California, San Francisco, CA, USA.
  • Bueno R; Diabetes Center, University of California, San Francisco, CA, USA.
  • Lee DS; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
  • Greenland JR; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Sun Y; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
  • Perez R; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France.
  • Ogorodnikov A; University of Paris, Imagine Institute, Paris, France.
  • Ward A; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Mann SA; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Lynch KL; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
  • Yun C; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Havlir DV; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
  • Chamie G; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Marquez C; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
  • Greenhouse B; ImmunoX Initiative, University of California, San Francisco, CA, USA.
  • Lionakis MS; Department of Medicine, San Francisco VA Health Care System, University of California, San Francisco, CA, USA.
  • Norris PJ; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Dumont LJ; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
  • Kelly K; ImmunoX Initiative, University of California, San Francisco, CA, USA.
  • Zhang P; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Zhang Q; School of Medicine, University of California, San Francisco, San Francisco, California, USA.
  • Gervais A; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Le Voyer T; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
  • Whatley A; Institute of Human Genetics, University of California, San Francisco, CA, USA.
  • Si Y; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA.
  • Byrne A; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA.
  • Combes AJ; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Rao AA; Zuckerberg San Francisco General, San Francisco, CA, USA.
  • Song YS; Zuckerberg San Francisco General, San Francisco, CA, USA.
  • Fragiadakis GK; Division of HIV, Infectious Disease and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
  • Kangelaris K; Division of HIV, Infectious Disease and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
  • Calfee CS; Division of HIV, Infectious Disease and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
  • Erle DJ; Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
  • Hendrickson C; Zuckerberg San Francisco General, San Francisco, CA, USA.
  • Krummel MF; Department of Laboratory Medicine, University of California, San Francisco, CA, USA.
  • Woodruff PG; Vitalant Research Institute, San Francisco, CA, USA.
  • Langelier CR; Vitalant Research Institute, Denver, CO, USA.
  • Casanova JL; University of Colorado School of Medicine, Aurora, CO, USA.
  • Derisi JL; Geisel School of Medicine at Dartmouth, Lebanon, NH, USA.
  • Anderson MS; Vitalant Research Institute, Denver, CO, USA.
  • Ye CJ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
bioRxiv ; 2021 Mar 10.
Article in En | MEDLINE | ID: mdl-33758859
Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Risk_factors_studies Language: En Journal: BioRxiv Year: 2021 Document type: Article Affiliation country: Netherlands Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Risk_factors_studies Language: En Journal: BioRxiv Year: 2021 Document type: Article Affiliation country: Netherlands Country of publication: United States