Extracellular vesicles released upon stimulation with antiphospholipid antibodies : An actual direct procoagulant mechanism or a new factor in the lupus anticoagulant paradox?

dc.creatorÁlvarez Jaramillo, Daniel
dc.creatorRúa Molina, Diana Carolina
dc.creatorVelásquez Berrío, Manuela
dc.creatorCataño Bedoya, John Ubeimar
dc.creatorEscudero, Carlos Alonso
dc.creatorCadavid Jaramillo, Ángela Patricia
dc.date2022-10-27T17:25:24Z
dc.date2022-10-27T17:25:24Z
dc.date2022
dc.date.accessioned2023-08-28T20:07:17Z
dc.date.available2023-08-28T20:07:17Z
dc.identifierÁlvarez D, Rúa C, Velásquez Berrío M, Cataño JU, Escudero C, Cadavid J ÁP. Extracellular vesicles released upon stimulation with antiphospholipid antibodies: An actual direct procoagulant mechanism or a new factor in the lupus anticoagulant paradox? J Autoimmun. 2022 Sep 15;133:102905. doi: 10.1016/j.jaut.2022.102905. Epub ahead of print. PMID: 36115210.
dc.identifier0896-8411
dc.identifierhttps://hdl.handle.net/10495/31499
dc.identifier10.1016/j.jaut.2022.102905
dc.identifier1095-9157
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8474176
dc.descriptionABSTRACT: Antiphospholipid antibodies (aPL) lead to a hypercoagulable state in vivo. Paradoxically, some of these autoantibodies perform as inhibitors of the coagulation cascade in vitro (a phenomenon referred to as “lupus anticoagulant”). The presence of lupus anticoagulant has been related to an increased quantity of plasma extracellular vesicles, which may constitute a direct procoagulant mechanism in antiphospholipid syndrome. This study investigates whether or not endothelial cell-derived extracellular vesicles released upon stimulation with aPL (aPL-EDEVs) are related to a higher direct coagulation activity. Using an in vitro model of endothelium, flow cytometry and a recalcified plasma-based assay, we found that the coagulation activity of aPL-EDEVs is mainly conditioned by the lupus anticoagulant-like activity of autoantibodies. Nevertheless, in the presence of β2 glycoprotein I, a cofactor of aPL during the stimulation of endothelial cells, the coagulation activity of EDEVs is restored in a mitogen-activated protein kinase kinases 1 and 2 (MEK1/2)-dependent manner. This phenomenon was especially evident when using immunoglobulins G from patients with vascular and obstetric primary antiphospholipid syndrome who manifest refractoriness to treatment. Our findings suggest that the role of aPL-EDEVs in the antiphospholipid syndrome-related hypercoagulable state may not rely on their capacity to enhance clotting directly. While β2 glycoprotein I performs as a procoagulant cofactor and restores the coagulation activity of extracellular vesicles via MEK1/2 pathway, proportionally, autoantibodies interact with aPL-EDEVs and exhaust their coagulation properties. Further analysis is required to establish whether lupus anticoagulant-like autoantibodies opsonise extracellular vesicles and whether opsonised vesicles may lead to thrombosis by indirect means.
dc.descriptionCOL0007631
dc.descriptionCOL0010421
dc.format12
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherElsevier
dc.publisherGrupo de Investigación en Trombosis
dc.publisherGrupo Reproducción
dc.publisherLondres, Inglaterra
dc.relationJ. Autoimmun.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAnticuerpos Antifosfolípidos
dc.subjectAntibodies, Antiphospholipid
dc.subjectInhibidor de Coagulación del Lupus
dc.subjectLupus Coagulation Inhibitor
dc.subjectQuinasas de Proteína Quinasa Activadas por Mitógenos
dc.subjectMitogen-Activated Protein Kinase Kinases
dc.subjectSíndrome Antifosfolípido
dc.subjectAntiphospholipid Syndrome
dc.subjectTrombosis
dc.subjectThrombosis
dc.subjectVesículas Extracelulares
dc.subjectExtracellular Vesicles
dc.titleExtracellular vesicles released upon stimulation with antiphospholipid antibodies : An actual direct procoagulant mechanism or a new factor in the lupus anticoagulant paradox?
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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