Open AccessEffects of anti‐β2 GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS 13 activity
Author(s) -
Ng Christopher J.,
McCrae Keith R.,
Ashworth Katrina,
Sosa Lucas J.,
Betapudi Venkaiah,
MancoJohnson Marilyn J.,
Liu Alice,
Dong JingFei,
Chung Dominic,
WhiteAdams Tara C.,
López José A.,
Di Paola Jorge
Publication year - 2018
Publication title -
research and practice in thrombosis and haemostasis
Language(s) - English
Resource type - Journals
ISSN - 2475-0379
DOI - 10.1002/rth2.12090
Subject(s) - von willebrand factor , adamts13 , umbilical vein , autoantibody , antibody , platelet , human umbilical vein endothelial cell , endothelial stem cell , immunology , endothelium , chemistry , microbiology and biotechnology , medicine , biology , in vitro , biochemistry
Essentials The antiphospholipid syndrome predisposes to thrombosis due to activation of endothelium and blood components. The role of anti‐β2GPI antibodies in VWF release and ADAMTS13 function is not well understood. Some anti‐β2GPI antibodies induce endothelial release of soluble VWF but not VWF strings. An anti‐β2GPI antibody can decrease ADAMTS13 activity in vitro similar to ex vivo results.Background Antiphospholipid syndrome ( APS ) is characterized by recurrent thromboembolic events in the setting of pathologic autoantibodies, some of which are directed to β2‐Glycoprotein 1 (β2 GPI ). The mechanisms of thrombosis in APS appear to be multifactorial and likely include a component of endothelial activation. Among other things, activated endothelium secretes von Willebrand factor, a hemostatic protein that in excess can increase the risk of thrombosis. Objective We hypothesized that anti‐β2 GPI antibodies could regulate the release and modulation of VWF from endothelial cells. Patients/Methods Isolated anti‐β2 GPI antibodies from patients with APS were assayed for their ability to induced VWF release from HUVEC s and modulate the effects of ADAMTS 13 in a shear‐dependent assay. Results We observed that anti‐β2 GPI antibodies from some patients with APS induced VWF release from human endothelial cells but did not induce formation of cell‐anchored VWF ‐platelet strings. Finally, we also determined that one of the Anti‐β2 GPI antibodies tested can inhibit the function of ADAMTS 13, the main modulator of extracellular VWF . Conclusions These results suggest that VWF and ADAMTS 13 may play a role in the prothrombotic phenotype of APS .