tetano
Editor, Senior Moderator
Res Pract Thromb Haemost
. 2022 Dec 9;6(8):e12811.
doi: 10.1002/rth2.12811. eCollection 2022 Nov.
Platelet caspase-1 and Bruton tyrosine kinase activation in patients with COVID-19 is associated with disease severity and reversed in vitro by ibrutinib
Livia Claude[SUP] 1 2 3 4 [/SUP], Frédéric Martino[SUP] 1 5 [/SUP], Patricia Hermand[SUP] 2 3 4 [/SUP], Bassel Chahim[SUP] 6 [/SUP], Pierre-Marie Roger[SUP] 7 [/SUP], Marie de Bourayne[SUP] 8 [/SUP], Yohann Garnier[SUP] 1 2 3 4 [/SUP], Benoit Tressieres[SUP] 9 [/SUP], Yves Colin[SUP] 2 3 4 [/SUP], Caroline Le Van Kim[SUP] 2 3 4 [/SUP], Marc Romana[SUP] 1 2 3 4 [/SUP], Véronique Baccini[SUP] 1 2 3 4 10 [/SUP]
Affiliations
Abstract
Background: Severity of coronavirus disease 2019 (COVID-19) is often associated with thrombotic complications and cytokine storm leading to intensive are unit (ICU) admission. Platelets are known to be responsible for abnormal hemostasis parameters (thrombocytopenia, raised D-dimers, and prolonged prothrombin time) in other viral infections through the activation of the nucleotide-binding domain leucine repeat rich containing protein 3 inflammasome induced by signaling pathways driven by Bruton tyrosine kinase (BTK) and leading to caspase-1 activation.
Objectives: We hypothesized that caspase-1 activation and the phosphorylation of BTK could be associated with the severity of the disease and that ibrutinib, a BTK inhibitor, could inhibit platelet activation.
Methods and results: We studied caspase-1 activation by flow cytometry and the phosphorylation of BTK by Western blot in a cohort of 51 Afro-Carribean patients with COVID-19 disease (19 not treated in ICU and 32 treated in ICU). Patients with a platelet count of 286.7 × 10[SUP]9[/SUP]/L (69-642 × 10[SUP]9[/SUP]/L) were treated by steroids and heparin preventive anticoagulation. Caspase-1 and BTK activation were associated with the severity of the disease and with the procoagulant state of the patients. Furthermore, we showed in vitro that the plasma of ICU patients with COVID-19 was able to increase CD62P expression and caspase-1 activity of healthy platelets and that ibrutinib could prevent it.
Conclusions: Our results show that caspase-1 and BTK activation are related to disease severity and suggest the therapeutic hope raised by ibrutinib in the treatment of COVID-19 by reducing the procoagulant state of the patients.
Keywords: Bruton tyrosine kinase; COVID‐19; caspase‐1; ibrutinib; platelets.
. 2022 Dec 9;6(8):e12811.
doi: 10.1002/rth2.12811. eCollection 2022 Nov.
Platelet caspase-1 and Bruton tyrosine kinase activation in patients with COVID-19 is associated with disease severity and reversed in vitro by ibrutinib
Livia Claude[SUP] 1 2 3 4 [/SUP], Frédéric Martino[SUP] 1 5 [/SUP], Patricia Hermand[SUP] 2 3 4 [/SUP], Bassel Chahim[SUP] 6 [/SUP], Pierre-Marie Roger[SUP] 7 [/SUP], Marie de Bourayne[SUP] 8 [/SUP], Yohann Garnier[SUP] 1 2 3 4 [/SUP], Benoit Tressieres[SUP] 9 [/SUP], Yves Colin[SUP] 2 3 4 [/SUP], Caroline Le Van Kim[SUP] 2 3 4 [/SUP], Marc Romana[SUP] 1 2 3 4 [/SUP], Véronique Baccini[SUP] 1 2 3 4 10 [/SUP]
Affiliations
- PMID: 36514346
- PMCID: PMC9732813
- DOI: 10.1002/rth2.12811
Abstract
Background: Severity of coronavirus disease 2019 (COVID-19) is often associated with thrombotic complications and cytokine storm leading to intensive are unit (ICU) admission. Platelets are known to be responsible for abnormal hemostasis parameters (thrombocytopenia, raised D-dimers, and prolonged prothrombin time) in other viral infections through the activation of the nucleotide-binding domain leucine repeat rich containing protein 3 inflammasome induced by signaling pathways driven by Bruton tyrosine kinase (BTK) and leading to caspase-1 activation.
Objectives: We hypothesized that caspase-1 activation and the phosphorylation of BTK could be associated with the severity of the disease and that ibrutinib, a BTK inhibitor, could inhibit platelet activation.
Methods and results: We studied caspase-1 activation by flow cytometry and the phosphorylation of BTK by Western blot in a cohort of 51 Afro-Carribean patients with COVID-19 disease (19 not treated in ICU and 32 treated in ICU). Patients with a platelet count of 286.7 × 10[SUP]9[/SUP]/L (69-642 × 10[SUP]9[/SUP]/L) were treated by steroids and heparin preventive anticoagulation. Caspase-1 and BTK activation were associated with the severity of the disease and with the procoagulant state of the patients. Furthermore, we showed in vitro that the plasma of ICU patients with COVID-19 was able to increase CD62P expression and caspase-1 activity of healthy platelets and that ibrutinib could prevent it.
Conclusions: Our results show that caspase-1 and BTK activation are related to disease severity and suggest the therapeutic hope raised by ibrutinib in the treatment of COVID-19 by reducing the procoagulant state of the patients.
Keywords: Bruton tyrosine kinase; COVID‐19; caspase‐1; ibrutinib; platelets.