Aberrant glycosylation of anti-SARS-CoV-2 spike IgG is a pro-thrombotic stimulus for platelets

Bye, A. P. ORCID: https://orcid.org/0000-0002-2061-2253, Hoepel, W., Mitchell, J. L., Jegouic, S. M., Loureiro, S. ORCID: https://orcid.org/0009-0000-8886-6893, Sage, T., Vidarsson, G., Nouta, J., Wuhrer, M., de Taeye, S. W., van Gils, M., Kriek, N., Cooper, N., Jones, I. ORCID: https://orcid.org/0000-0002-7738-2516, den Dunnen, J. and Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352 (2021) Aberrant glycosylation of anti-SARS-CoV-2 spike IgG is a pro-thrombotic stimulus for platelets. Blood, 138 (16). pp. 1481-1489. ISSN 0006-4971 doi: 10.1182/blood.2021011871

Abstract/Summary

A subset of patients with COVID-19 become critically ill, suffering from severe respiratory problems and also increased rates of thrombosis. The causes of thrombosis in severely ill COVID-19 patients are still emerging, but the coincidence of critical illness with the timing of the onset of adaptive immunity could implicate an excessive immune response. We hypothesised that platelets might be susceptible to activation by anti-SARS-CoV-2 antibodies and contribute to thrombosis. We found that immune complexes containing recombinant SARS-CoV-2 spike protein and anti-spike IgG enhanced platelet-mediated thrombosis on von Willebrand Factor in vitro, but only when the glycosylation state of the Fc domain was modified to correspond with the aberrant glycosylation previously identified in patients with severe COVID-19. Furthermore, we found that activation was dependent on FcγRIIA and we provide in vitro evidence that this pathogenic platelet activation can be counteracted by therapeutic small molecules R406 (fostamatinib) and ibrutinib that inhibit tyrosine kinases Syk and Btk respectively or by the P2Y12 antagonist cangrelor.

Item Type	Article
URI	https://reading-pure-test.eprints-hosting.org/id/eprint/99392
Identification Number/DOI	10.1182/blood.2021011871
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences Central Services Life Sciences > School of Biological Sciences
Download/View statistics	View download statistics for this item