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.

Rights

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Cite as

Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) Covid BioResource Collaboration, Wang, Jun, Kotagiri, P., Lyons, P., Al-Lamki, R., Mescia, F., Bergamaschi, L., Turner, L., Morgan, M., Calero-Nieto, F., Bach, K., Mende, N., Wilson, N., Watts, E., Maxwell, P., Chinnery, P., Kingston, N., Papadia, S., Stirrups, K., Walker, N., Gupta, R., Menon, D., Allinson, K., Aitken, S., Toshner, M., Weekes, M., Nathan, J., Walmsley, S., Ouwehand, W., Kasanicki, M., Göttgens, B., Marioni, J., Smith, K., Pober, J. & Bradley, J. 2022, 'Coagulation factor V is a T-cell inhibitor expressed by leukocytes in COVID-19', iScience, 25(3), article no: 103971. https://doi.org/10.1016/j.isci.2022.103971

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Last updated: 12 October 2024
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