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IgG in patients with SLE without APS. FXa signalling has been observed in different cells, via activation of protease-activated receptors (PAR) which stimulates intracellular calcium (Ca2þ) release. Ca2þ regulates many cellular processes and changes in its signalling may trigger several pathological changes. Given that cellular responses elicited through activation of PARs are important in influencing pathways responsible for inflammation, tissue repair and haemostasis, FXa-reactive IgG may be important in the pathogenesis of SLE and APS. Therefore, we characterized the interaction between FXa and human umbilical vein endothelial cells (HUVEC) and the cellular effects of anti-FXa IgG isolated from patients with APS and SLE without APS. Methods: IgG was purified from patients with APS (n 1⁄4 14) and SLE/no APS (n 1⁄4 14) who had anti-FXa IgG and healthy controls (HC) (n 1⁄4 8). The effect of IgGs on FXa-mediated intracellular calcium release was measured and quantified using the fluorescent image plate reader. HUVECs were seeded in 96-well plates, for 48 h and then incubated with Fluo-4AM calcium binding dye. Alterations in intracellular calcium release were monitored following stimulation with a-thrombin (Thr) or FXa IgGs. PAR inhibitors, agonist peptides (AP), HCQ, fluvastatin and desensitization experiments were also performed to characterize responses. Results: We observed a dose-dependent induction of Ca2þ transients by FXa in HUVECS. FXa was a weaker agonist than Thr but the kinetics of response was different. APS IgG significantly potentiated the FXa-induced Ca2þ release compared with SLE IgG (P 1⁄4 0.04), HC IgG (P < 0.05) and FXa alone (P<0.05). FXa-mediated Ca2þ release was significantly reduced by PAR-1 inhibitors. When PAR-1 receptors were desensitized by Thr and cells were stimulated by PAR-2 AP, PAR-2 response was reduced by 47.5%. When Thr-desensitized cells were stimulated by FXa, response was reduced by 66% and residual response was not inhibited by PAR-1 or completely by 2 inhibitors. IgG potentiation was lost on Thr-desensitized cells. When cells were treated with a specific FXa inhibitor, HCQ or fluvastatin, FXa induced and IgG potentiated intracellular Ca2þ release was significantly reduced. Conclusion: FXa stimulation of HUVEC was mediated mainly via PAR1 and 2 dependent signalling mechanisms and this effect was enhanced by FXa-reactive APS-IgG. These effects were blocked by an FXa inhibitor which raises the exciting prospect that anti-FXa IgG positivity may be used as a novel biomarker to predict response to treatment with FXa inhibitors in APS. Despite the need for the specificity to be investigated further, results also suggest that HCQ and fluvastatin may be beneficial in patients with APS. Disclosure statement: The authors have declared no conflicts of interest. O60 EXTRA-CORPOREAL MEMBRANE OXYGENATION AND DIFFUSE ALVEOLAR HAEMORRHAGE IN SYSTEMIC VASCULITIDES: A SINGLE CENTRE CASE SERIES AND ANALYSIS OF THE ELSO DATABASE

rheumatology

O60 Extra-Corporeal Membrane Oxygenation and Diffuse Alveolar Haemorrhage in Systemic Vasculitides: A Single Centre Case Series and Analysis of the Elso Database