Article Dans Une Revue Haematologica Année : 2022

The deglycosylated form of 1E12 inhibits platelet activation and prothrombotic effects induced by VITT antibodies.

Résumé

In order to improve the safety of COVID-19 vaccines, there is an urgent need to unravel the pathogenesis of vaccineinduced immune thrombotic thrombocytopenia (VITT), a severe complication of recombinant adenoviral vector vaccines used to prevent COVID-19, and likely due to anti-platelet factor 4 (PF4) IgG antibodies. In this study, we demonstrated that 1E12, a chimeric anti-PF4 antibody with a human Fc fragment, fully mimics the effects of human VITT antibodies, as it activates platelets to a similar level in the presence of platelet factor 4 (PF4). Incubated with neutrophils, platelets and PF4, 1E12 also strongly induces NETosis, and in a microfluidic model of whole blood thrombosis, it triggers the formation of large platelet/leukocyte thrombi containing fibrin(ogen). In addition, a deglycosylated form of 1E12 (DG-1E12), which still binds PF4 but no longer interacts with Fcγ receptors, inhibits platelet, granulocyte and clotting activation induced by human anti-PF4 VITT antibodies. This strongly supports that 1E12 and VITT antibodies recognize overlapping epitopes on PF4. In conclusion, 1E12 is a potentially important tool to study the pathophysiology of VITT, and for establishing mouse models. On the other hand, DG-1E12 may help the development of a new drug that specifically neutralizes the pathogenic effect of autoimmune anti-PF4 antibodies, such as those associated with VITT.

Dates et versions

hal-04845216 , version 1 (18-12-2024)

Identifiants

Citer

C. Vayne, R. Palankar, S. Billy, S. Handtke, T. Thiele, et al.. The deglycosylated form of 1E12 inhibits platelet activation and prothrombotic effects induced by VITT antibodies.. Haematologica, 2022, Haematologica, 107 (10), pp.2445-2453. ⟨10.3324/haematol.2021.280251⟩. ⟨hal-04845216⟩
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