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Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19.
Wang, Jun; Kotagiri, Prasanti; Lyons, Paul A; Al-Lamki, Rafia S; Mescia, Federica; Bergamaschi, Laura; Turner, Lorinda; Morgan, Michael D; Calero-Nieto, Fernando J; Bach, Karsten; Mende, Nicole; Wilson, Nicola K; Watts, Emily R; Maxwell, Patrick H; Chinnery, Patrick F; Kingston, Nathalie; Papadia, Sofia; Stirrups, Kathleen E; Walker, Neil; Gupta, Ravindra K; Menon, David K; Allinson, Kieren; Aitken, Sarah J; Toshner, Mark; Weekes, Michael P; Nathan, James A; Walmsley, Sarah R; Ouwehand, Willem H; Kasanicki, Mary; Göttgens, Berthold; Marioni, John C; Smith, Kenneth G C; Pober, Jordan S; Bradley, John R.
  • Wang J; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
  • Kotagiri P; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
  • Lyons PA; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK.
  • Al-Lamki RS; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
  • Mescia F; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK.
  • Bergamaschi L; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
  • Turner L; Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
  • Morgan MD; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
  • Calero-Nieto FJ; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK.
  • Bach K; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
  • Mende N; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK.
  • Wilson NK; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
  • Watts ER; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK.
  • Maxwell PH; Department of Haematology, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Chinnery PF; Department of Haematology, Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, Cambridgeshire CB2 0AW, UK.
  • Kingston N; Cancer Research UK -Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK.
  • Papadia S; Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
  • Stirrups KE; Department of Haematology, Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, Cambridgeshire CB2 0AW, UK.
  • Walker N; Department of Haematology, Wellcome and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, Cambridgeshire CB2 0AW, UK.
  • Gupta RK; Centre for Inflammation Research, Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK.
  • Allinson K; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
  • Aitken SJ; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Toshner M; Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Weekes MP; Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0XY, UK.
  • Nathan JA; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Walmsley SR; Department of Haematology, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Ouwehand WH; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Kasanicki M; Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Göttgens B; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Marioni JC; Department of Haematology, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Smith KGC; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Pober JS; Department of Haematology, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Bradley JR; Department of Medicine, University of Cambridge, Addenbrookes Hospital, Box 157, Hills Rd, Cambridge CB2 0QQ, UK.
iScience ; 25(3): 103971, 2022 Mar 18.
Article in English | MEDLINE | ID: covidwho-1699877
ABSTRACT
Clotting Factor V (FV) is primarily synthesized in the liver and when cleaved by thrombin forms pro-coagulant Factor Va (FVa). Using whole blood RNAseq and scRNAseq of peripheral blood mononuclear cells, we find that FV mRNA is expressed in leukocytes, and identify neutrophils, monocytes, and T regulatory cells as sources of increased FV in hospitalized patients with COVID-19. Proteomic analysis confirms increased FV in circulating neutrophils in severe COVID-19, and immunofluorescence microscopy identifies FV in lung-infiltrating leukocytes in COVID-19 lung disease. Increased leukocyte FV expression in severe disease correlates with T-cell lymphopenia. Both plasma-derived and a cleavage resistant recombinant FV, but not thrombin cleaved FVa, suppress T-cell proliferation in vitro. Anticoagulants that reduce FV conversion to FVa, including heparin, may have the unintended consequence of suppressing the adaptive immune system.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2022.103971

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Full text: Available Collection: International databases Database: MEDLINE Language: English Journal: IScience Year: 2022 Document Type: Article Affiliation country: J.isci.2022.103971