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dc.contributor.author | Andrianova I. | |
dc.contributor.author | Ponomareva A. | |
dc.contributor.author | Mordakhanova E. | |
dc.contributor.author | Le Minh G. | |
dc.contributor.author | Daminova A. | |
dc.contributor.author | Nevzorova T. | |
dc.contributor.author | Rauova L. | |
dc.contributor.author | Litvinov R. | |
dc.contributor.author | Weisel J. | |
dc.date.accessioned | 2020-01-21T20:38:48Z | |
dc.date.available | 2020-01-21T20:38:48Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0896-8411 | |
dc.identifier.uri | https://dspace.kpfu.ru/xmlui/handle/net/157542 | |
dc.description.abstract | © 2019 Elsevier Ltd Systemic lupus erythematosus (SLE) is associated with a high risk of venous and arterial thrombosis, not necessarily associated with prothrombotic antiphospholipid antibodies (Abs). Alternatively, thrombosis may be due to an increased titer of anti-dsDNA Abs that presumably promote thrombosis via direct platelet activation. Here, we investigated effects of purified anti-dsDNA Abs from the blood of SLE patients, alone or in a complex with dsDNA, on isolated normal human platelets. We showed that anti-dsDNA Abs and anti-dsDNA Ab/dsDNA complexes induced strong platelet activation assessed by enhanced P-selectin expression and dramatic morphological and ultrastructural changes. Electron microscopy revealed a significantly higher percentage of platelets that lost their discoid shape, formed multiple filopodia and had a shrunken body when treated with anti-dsDNA Abs or anti-dsDNA Ab/dsDNA complexes compared with control samples. In addition, these platelets activated with anti-dsDNA Ab/dsDNA complexes typically contained a reduced number of secretory α-granules that grouped in the middle and often merged into a solid electron dense area. Many activated platelets released plasma membrane-derived microvesicles and/or fell apart into subcellular cytoplasmic fragments. Confocal microscopy revealed that platelets treated with anti-dsDNA Ab/dsDNA complex had a heterogeneous distribution of septin2 compared with the homogeneous distribution in control platelets. Structural perturbations were concomitant with mitochondrial depolarization and a decreased content of platelet ATP, indicating energetic exhaustion. Most of the biochemical and morphological changes in platelets induced by anti-dsDNA Abs and anti-dsDNA Ab/dsDNA complexes were prevented by pre-treatment with a monoclonal mAb against FcγRIIA. The aggregate of data indicates that anti-dsDNA Abs alone or in a complex with dsDNA strongly affect platelets via the FcγRIIA receptor. The immune activation of platelets with antinuclear Abs may comprise a prothrombotic mechanism underlying a high risk of thrombotic complications in patients with SLE. | |
dc.relation.ispartofseries | Journal of Autoimmunity | |
dc.subject | anti-dsDNA-antibodies | |
dc.subject | Platelet | |
dc.subject | Systemic lupus erythematosus | |
dc.subject | Thrombosis | |
dc.title | In systemic lupus erythematosus anti-dsDNA antibodies can promote thrombosis through direct platelet activation | |
dc.type | Article | |
dc.collection | Публикации сотрудников КФУ | |
dc.source.id | SCOPUS08968411-2019-SID85075483240 |