Remy Martins-Gonçalves, Stephane Vicente Rozini, Daniela P Mendes-de-Almeida, Lohanna Palhinha, Carolina Q Sacramento, Gean Carlo Pereira-Silva, Mariana M Campos, Douglas Mathias de Oliveira, Carlos A Lopes-Cardoso E Souza, Beatriz de Barros Gonçalves de Jesus, Isaclaudia Gomes de Azevedo-Quintanilha, Patricia Mouta Nunes de Oliveira, Renata Saraiva Pedro, Letícia Kegele Lignani, Gabriellen Vitiello Teixeira, Joanna Bokel, Sandra Wagner Cardoso, Brenda Hoagland, Elvira M Saraiva, Beatriz Grinsztejn, Maria de Lourdes de Sousa Maia, Luiz Amorim Filho, Eugenio D Hottz, Patricia T Bozza
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引用次数: 0
Abstract
Background: Although rare, vaccine-induced thrombotic thrombocytopenia (VITT) following adenoviral vector COVID-19 vaccination is a concerning and often severe adverse effect of vaccination. The generation of high anti-platelet factor 4 (PF4) antibody titers, promotes the formation of immune complexes capable of activating platelets and neutrophils through FcγRIIa.
Objective: Given that Platelet-leukocyte aggregate (PLA) formation and inflammasome activation are common features of thromboinflammatory diseases, we aimed to evaluate if these are also features of VITT.
Methods: Samples from a cohort of 57 postvaccination thrombosis patients and 28 age- and sex-matched unvaccinated individuals were used for ex-vivo investigation of PLA formation and inflammasome activation.
Results: Patients with clinical features of VITT presented elevated levels of activated caspase-1, IL-18 and IL-1β in the plasma. We also found that soluble factors in the plasma of VITT patients induce the formation of platelet-neutrophil aggregates but not platelet-monocyte or platelet-T-cell aggregates, which are associated with increased caspase-1 activation in neutrophils ex-vivo. Platelet-neutrophil aggregate formation was prevented through blockage of FcγRIIa with the neutralizing antibody IV.3, and through blockage of P-selectin or integrin αIIbβ3, also inhibiting caspase-1 activation. Additionally, MCC950, an NLRP3 inflammasome inhibitor, blocked caspase-1 activation.
Conclusions: Taken together, these data show that VITT plasma induces platelet-neutrophil aggregate formation in an FcγRIIa-dependent manner and that platelet-neutrophil interactions may contribute to thromboinflammation in VITT patients by supporting NLRP3 inflammasome activation. These data shed light on novel immunopathological events associated with inflammation and thrombosis in VITT patients.
期刊介绍:
The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community.
Types of Publications:
The journal publishes a variety of content, including:
Original research reports
State-of-the-art reviews
Brief reports
Case reports
Invited commentaries on publications in the Journal
Forum articles
Correspondence
Announcements
Scope of Contributions:
Editors invite contributions from both fundamental and clinical domains. These include:
Basic manuscripts on blood coagulation and fibrinolysis
Studies on proteins and reactions related to thrombosis and haemostasis
Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms
Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases
Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.