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Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19
Monique G.P. van der Wijst; Sara E. Vazquez; George C. Hartoularos; Paul Bastard; Tianna Grant; Raymund Bueno; David S. Lee; John R. Greenland; Yang Sun; Richard Perez; Anton Ogorodnikov; Alyssa Ward; Sabrina A. Mann; Kara L. Lynch; Cassandra Yun; Diane V. Havlir; Gabriel Chamie; Carina Marquez; Bryan Greenhouse; Michail S. Lionakis; Philip J. Norris; Larry J. Dumont; Kathleen Kelly; Peng Zhang; Qian Zhang; Adrian Gervais; Tom Le Voyer; Alexander Whatley; Yichen Si; Ashley Byrne; Alexis J. Combes; Arjun Arkal; Yun S. Song; Gabriela K. Fragiadakis; - UCSF COMET consortium; Kirsten Kangelaris; Carolyn S. Calfee; David J. Erle; Carolyn Hendrickson; Matthew F. Krummel; Prescott G. Woodruff; Charles R. Langelier; Jean-Laurent Casanova; Joseph L. Derisi; Mark S. Anderson; Chun J. Ye.
Afiliação
  • Monique G.P. van der Wijst; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherland; Institute of Human Genetics, University of Cali
  • Sara E. Vazquez; Medical Scientist Training Program, University of California. San Francisco, CA, USA; Tetrad Graduate Program, University of California, San Francisco, CA, USA;
  • George C. Hartoularos; Institute of Human Genetics, University of California, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San F
  • Paul Bastard; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine
  • Tianna Grant; Institute of Human Genetics, University of California, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San F
  • Raymund Bueno; Institute of Human Genetics, University of California, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San F
  • David S. Lee; Institute of Human Genetics, University of California, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San F
  • John R. Greenland; Department of Medicine, San Francisco VA Health Care System, University of California, San Francisco, CA, USA.
  • Yang Sun; Institute of Human Genetics, University of California, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San F
  • Richard Perez; Institute of Human Genetics, University of California, San Francisco, CA, USA; School of Medicine, University of California, San Francisco, San Francisco, Calif
  • Anton Ogorodnikov; Institute of Human Genetics, University of California, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San F
  • Alyssa Ward; Institute of Human Genetics, University of California, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San F
  • Sabrina A. Mann; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Kara L. Lynch; Zuckerberg San Francisco General, San Francisco, CA, USA.
  • Cassandra Yun; Zuckerberg San Francisco General, San Francisco, CA, USA.
  • Diane V. Havlir; Division of HIV, Infectious Disease and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
  • Gabriel Chamie; Division of HIV, Infectious Disease and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
  • Carina Marquez; Division of HIV, Infectious Disease and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
  • Bryan Greenhouse; Division of HIV, Infectious Disease and Global Medicine, Department of Medicine, University of California, San Francisco, CA, USA.
  • Michail S. Lionakis; Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Ins
  • Philip J. Norris; Zuckerberg San Francisco General, San Francisco, CA, USA; Department of Laboratory Medicine, University of California, San Francisco, CA, USA; Vitalant Research
  • Larry J. Dumont; Vitalant Research Institute, Denver, CO, USA; University of Colorado School of Medicine, Aurora, CO, USA; Geisel School of Medicine at Dartmouth, Lebanon, NH, U
  • Kathleen Kelly; Vitalant Research Institute, Denver, CO, USA.
  • Peng Zhang; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Qian Zhang; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA.
  • Adrian Gervais; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller Univer
  • Tom Le Voyer; University of Paris, Imagine Institute, Paris, France; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller Univer
  • Alexander Whatley; Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA.
  • Yichen Si; Department of Biostaticstics, University of Michigan.
  • Ashley Byrne; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Alexis J. Combes; ImmunoX Initiative, University of California, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, CA, USA; UCSF CoLabs, Un
  • Arjun Arkal; ImmunoX Initiative, University of California, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, CA, USA; UCSF CoLabs, Un
  • Yun S. Song; Chan Zuckerberg Biohub, San Francisco, CA, USA; Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA; Departm
  • Gabriela K. Fragiadakis; Division of Rheumatology, Department of Medicine, University of California, San Francisco, California, USA; ImmunoX Initiative, University of California, San Fr
  • - UCSF COMET consortium; -
  • Kirsten Kangelaris; Division of Infectious Disease, Department of Medicine, University of California, San Francisco, CA, USA.
  • Carolyn S. Calfee; Division of Pulmonary and Critical Care Medicine, Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, CA,
  • David J. Erle; Institute of Human Genetics, University of California, San Francisco, CA, USA; ImmunoX Initiative, University of California, San Francisco, CA, USA; Zuckerberg
  • Carolyn Hendrickson; Division of Pulmonary and Critical Care Medicine, Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, CA,
  • Matthew F. Krummel; ImmunoX Initiative, University of California, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, CA, USA.
  • Prescott G. Woodruff; ImmunoX Initiative, University of California, San Francisco, CA, USA; Division of Pulmonary and Critical Care Medicine, Department of Medicine and the Cardiovas
  • Charles R. Langelier; Division of Infectious Disease, Department of Medicine, University of California, San Francisco, CA, USA.
  • Jean-Laurent Casanova; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France; University of Paris, Imagine
  • Joseph L. Derisi; Department of Biochemistry and Biophysics, University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA.
  • Mark S. Anderson; Diabetes Center, University of California, San Francisco, CA, USA; Endocrine Division, Department of Medicine, University of California, San Francisco, CA, USA.
  • Chun J. Ye; Institute of Human Genetics, University of California, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San F
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-434529
ABSTRACT
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.
Licença
cc_by_nc_nd
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Tipo de estudo: Experimental_studies / Estudo observacional / Estudo prognóstico Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
Texto completo: Disponível Coleções: Preprints Base de dados: bioRxiv Tipo de estudo: Experimental_studies / Estudo observacional / Estudo prognóstico Idioma: Inglês Ano de publicação: 2021 Tipo de documento: Preprint
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