Effect of Anti-B2GPI Antibodies on VWF release from Human Umbilical Vein Endothelial Cells and Decrease ADAMTS13 activity

CHRISTOPHER J. NG; KEITH R. MCCRAE; KATRINA ASHWORTH; LUCAS J. SOSA; VENKAIAH BETAPUDI; MARILYN J. MANCO-JOHNSON; ALICE LIU; JING-FEI DONG; DOMINIC CHUNG; TARA C. WHITE-ADAMS; JOSÉ A. LÓPEZ ; JORGE DI PAOLA

Research and Practice in Thrombosis and Haemostasis

John Wiley & Sons, Inc.

Año: 2018

2475-0379

The 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 includes 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.We hypothesized that anti-β2GPI antibodies could regulate the release and modulation of VWF from endothelial cells. 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. These results suggest that VWF and ADAMTS13 may play a role in the prothrombotic phenotype of APS.