Association between extracellular vesicles (EVs) and thrombosis in antiphospholipid syndrome

Author(s)

Jacintho-Robison, Bruna Cardoso ; Oliveira, Jose Diogo ; Cesped, Lucas Matheus Bispo ; de Souza, Cristiane Maria ; Barion, Barbara Gomes ; Vaz, Camila de Oliveira ; Mazetto, Bruna De Moraes ; Orsi, Fernanda Andrade

• Document type: Journal article
• Source: Lupus; v. 34, n. 5, p. 11-pg., 2025-03-23.

Abstract

Background Antiphospholipid syndrome (APS) is characterized by thrombosis or pregnancy complications associated with the presence of antiphospholipid antibodies (aPLs). Although the exact mechanisms are unclear, aPLs can increase the expression of tissue factor on platelets, leukocytes, and endothelial cells, leading to hypercoagulability. Extracellular vesicles (EVs) can also be released during this process and play a key role in immune regulation and thrombosis related to APS.Aims To evaluate the association between circulating levels of EVs and thrombosis related to APS, as well as inflammatory markers.Methods Case-control study including patients with thrombotic APS (t-APS) and healthy controls (HC). EVs expressing the following antigens were quantified by flow cytometry: CD41 (platelet integrin alpha IIb), CD162 (P-selectin glycoprotein ligand 1), CD31 (platelet and endothelial cell adhesion molecule 1), CD142 (tissue factor), and CD62 (P-selectin). EV levels were compared between groups and correlated with APS clinical and inflammatory parameters.Results A total of 69 t-APS patients and 46 HC were included. CD162+EV, CD31+EV, and CD41+EV levels were higher in t-APS patients compared to controls. CD41+EV levels were associated with venous thrombosis (p = .04) and multiple thrombosis (p = .07). Levels of CD162+EV, CD31+EV, CD142+EV and CD62P + EV were positively correlated with levels of interleukin-1 beta (IL-1 beta).Conclusion EVs expressing antigens related to platelet and endothelial cell activation and adhesion, as well as platelet-leukocyte interaction, were associated with thrombosis related to APS. The correlation between EV levels and IL-1 beta levels further underscore the association between EV release and thromboinflammatory responses in APS. Our results demonstrate the involvement of EVs in the interaction between inflammation and thrombosis in APS. (AU)

• FAPESP's process: 22/13216-0 - Crosstalk between hemostasis and innate immunity (Immunothrombosis): pathogenic, diagnostic and therapeutic implications in infectious and inflammatory diseases
• Grantee: Erich Vinicius de Paula
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/13956-9 - Contribution of Neutrophil Extracellular Traps (NETs) and platelet activation to Immunothrombosis in COVID-19 and inhibitory effect of substances that increase intracellular levels of cyclic nucleotides
• Grantee: José Diogo Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 23/07899-0 - EXPLORATION OF PURINERGIC SIGNALING PATHWAYS AS A PLATELET ACTIVATION MECHANISM IN ANTIPHOSPHOLIPID SYNDROME
• Grantee: Bruna Cardoso Robison
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/12630-2 - Role of neutrophil extracellular traps (NETs) and platelet activation in immunothrombosis related to COVID-19 and inhibitory effect of substances that increase intracellular levels of cyclic nucleotides
• Grantee: Fernanda Loureiro de Andrade Orsi
• Support Opportunities: Regular Research Grants