Differential regulation of proinflammatory mediators following LPS- and ATP-induced activation of monocytes from patients with antiphospholipid syndrome.
Anush Martirosyan,Martin Petrek,Zdenka Navratilova,Armen Blbulyan,Anna Boyajyan,Gayane Manukyan,Gayane Manukyan +6 more
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TLDR
Increased sensitivity of APS cells to LPS that may contribute to thrombus formation and enhance development or progression of autoimmune processes is indicated.Abstract:
Antiphospholipid syndrome (APS) is an acquired autoimmune disorder characterized by recurrent thrombosis and pregnancy morbidity in association with the presence of antiphospholipid antibodies. Growing evidence supports the involvement of monocytes in APS pathogenesis. Inflammatory activation of monocytes promotes thrombus formation and other APS complications. However, mechanisms underlying their activation are poorly investigated. We aimed to determine transcriptional activity of monocytes after exposing them to low concentrations of lipopolysaccharide (LPS) and LPS + adenosine triphosphate (ATP) using comparative qRT-PCR. The results showed that LPS significantly increased transcriptional levels of TLR2, IL-23, CCL2, CXCL10, IL-1β, and IL-6 in APS cells, while, in cells from healthy donors, LPS resulted in IL-6 and STAT3 elevated mRNAs. Double stimulation of the cells resulted in decreased mRNA levels of NLRP3 in monocytes isolated from healthy donors and CCL2, IL-1β in APS cells. By contrast, TLR2 mRNAs were elevated in both investigated groups after culture of the cells with LPS + ATP. Thus, the findings indicate increased sensitivity of APS cells to LPS that may contribute to thrombus formation and enhance development or progression of autoimmune processes. Low concentrations of ATP diminish LPS-induced inflammatory state of APS monocytes which might be a potential mechanism which regulates inflammatory state of the cells.read more
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Journal ArticleDOI
Circulating levels of tissue factor and the risk of thrombosis associated with antiphospholipid syndrome.
Laís Quinteiro Tobaldini,Fernanda Talge Arantes,Sabrina da Silva Saraiva,Bruna M Mazetto,Marina Pereira Colella,Erich Vinicius De Paula,Joyce Annichino-Bizzachi,Fernanda Andrade Orsi +7 more
TL;DR: Circulating TF is associated with thrombotic complications related to APS, but not with the risk of unprovoked VTE, as compared with controls.
Journal ArticleDOI
Immunosuppressive Treatment in Antiphospholipid Syndrome: Is It Worth It?
Ilaria Mormile,Francescopaolo Granata,Alessandra Punziano,Amato de Paulis,Francesca Wanda Rossi +4 more
TL;DR: A comprehensive review of literature analyzing the possible role of immunomodulation in primary antiphospholipid syndrome (APS) is presented in this paper, which provides a broad overview of potentially safe and effective target treatments for managing this devastating disease.
Book ChapterDOI
Mechanisms of Antiphospholipid Antibody-Mediated Thrombosis
Rohan Willis,Hannah Cohen,Ian Giles,Jason S. Knight,Steven A. Krilis,Anisur Rahman,Philip G. de Groot +6 more
TL;DR: This chapter outlines the mechanisms that contribute to thrombosis in APS and reviews the facets of this topic for which there is no consensus among experts in the field, for instance, the relative importance of various mechanisms in the precipitation of thromBosis.
Journal ArticleDOI
Anti-domain 1 β2 glycoprotein antibodies increase expression of tissue factor on monocytes and activate NK Cells and CD8+ cells in vitro
Gayane Manukyan,Anush Martirosyan,Ludek Slavik,Sona Margaryan,Jana Ulehlova,Zuzana Mikulková,Antonin Hlusi,Tomas Papajik,Eva Kriegova +8 more
TL;DR: The ability of patient-derived aPL to induce immune cell activation and TF expression on monocytes is shown and the influence of anti-D1 β2GPI on the activation status of monocytes, NK and cytotoxic T cells is demonstrated for the first time.
Journal ArticleDOI
miR-19b-3p and miR-20a-5p are associated with the levels of antiphospholipid antibodies in patients with antiphospholipid syndrome
Yaneli Juárez-Vicuña,Carlos Alfonso Guzmán-Martín,L A Martínez-Martínez,Adrián Hernández-Díazcouder,Claudia Huesca-Gómez,Ricardo Gamboa,Luis M. Amezcua-Guerra,M.J.N.N. Chacon-Perez,M C Amigo,Fausto Sánchez-Muñoz +9 more
TL;DR: In this paper, microRNA expression of miR19b-3p and miR-20a-5p was measured in monocytes by RT-qPCR.
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