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

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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.

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Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/99392
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR) Life Sciences > School of Biological Sciences > Biomedical Sciences
Uncontrolled Keywords	COVID-19, SARS-CoV2, thrombosis, platelets, IgG receptor, IgG glycosylation
Publisher	American Society of Hematology
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Funders:	British Heart Foundation	The sponsoring bodies who contributed funding for the creation of this item. Example: NERC Example: The Royal Society of Chemistry A pick list of funders may appear as you type in the funder's name in full or as an acronym. Select a correct match to complete the field or type in a new entry in full. For new entries, the full name is preferred.
Projects:	The physiological importance and integration of receptor-mediated inhibitory mechanisms in platelets in health and disease Funded by: British Heart Foundation (RG/15/2/31224 - £1,426,158) Local Lead (PI): Jon Gibbins 1 September 2015 - 31 August 2020	Click Add to select your project (received at Reading) from an autocomplete list.

Deposit Details

Date Deposited:	28 Jul 2021 12:26	Date item deposited into CentAUR
Last Modified:	25 Feb 2025 02:49	Date item last modified

References

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