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 |
|