Effects of anti‐β2GPI antibodies on VWF release from human umbilical vein endothelial cells and ADAMTS13 activity. Issue 2 (24th March 2018)

• Record Type: Journal Article
• Authors: Ng, Christopher J.; McCrae, Keith R.; Ashworth, Katrina; Sosa, Lucas J.; Betapudi, Venkaiah; Manco‐Johnson, Marilyn J.; Liu, Alice; Dong, Jing‐Fei; Chung, Dominic; White‐Adams, Tara C.; López, José A.; Di Paola, Jorge
• Is Part Of: Research and practice in thrombosis and haemostasis. Volume 2:Issue 2(2018)
• Page Start: 380
• Page End: 389
• Publication Date: 2018-03-24
• Subjects: ADAMTS13 -- antiphospholipid syndrome -- endothelial cells -- von Willebrand factor; Thrombosis -- Periodicals; Hemostasis -- Periodicals; 616.135005
• DOI: 10.1002/rth2.12090
• Languages: English
• ISSNs: 2475-0379

Abstract

Abstract: 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 (β2GPI). 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‐β2GPI antibodies could regulate the release and modulation of VWF from endothelial cells. Patients/Methods: Isolated anti‐β2GPI antibodies from patients with APS were assayed for their ability to induced VWF release from HUVECs and modulate the effects of ADAMTS13 in a shear‐dependent assay. Results: We observed that anti‐β2GPI 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‐β2GPI antibodies tested can inhibit the function of ADAMTS13, the main modulator of extracellular VWF. Conclusions: These results suggest that VWF and ADAMTS13 may play a role in the prothrombotic phenotype of APS.