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    Anti-factor Xa antibodies in patients with antiphospholipid syndrome and their effects upon coagulation assays

    Artim-Esen, B. and Pericleous, C. and Mackie, I. and Ripoll, V.M. and Latchman, David S. and Isenberg, D. and Rahman, A. and Ioannou, Y. and Giles, I. (2015) Anti-factor Xa antibodies in patients with antiphospholipid syndrome and their effects upon coagulation assays. Arthritis Research & Therapy 17 (1), ISSN 1478-6354.

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    Abstract

    - Introduction: The aim of this study was to examine the prevalence and functional effects of antibodies directed against Factor (F)Xa and other serine proteases (SP) in patients with antiphospholipid syndrome (APS). - Methods: Serum from patients with APS (n = 59), systemic lupus erythematosus (SLE; n = 106), other autoimmune rheumatic disease (ARD; n = 63) and 40 healthy controls (HC) were tested for IgG activity against thrombin (Thr), FXa, FVIIa, phosphatidylserine (PS)/FXa and antithrombin (AT)-III by enzyme-linked immunosorbent assay (ELISA). Anti-FXa positive IgG were purified to measure their avidity by chaotropic ELISA and functional effects upon clotting time (FXa-ACT) and FXa enzymatic activity (± AT-III). - Results: Anti-FXa IgG were found in patients with SLE (49.1%) and APS (33.9%) (P <0.05) but not in ARD controls and HC. In contrast, anti-Thr and anti-PS/FXa IgG were identified in other ARD and anti-FVIIa IgG were low in all groups. The avidity of APS-IgG to FXa was significantly higher than SLE-IgG (P <0.05). Greatest prolongation of FXa-ACT was observed with APS-IgG and greatest inhibitory effect upon FXa enzymatic activity was found with APS-IgG followed by SLE-IgG compared to HC-IgG. ATIII inhibition of FXa was significantly reduced by APS-IgG compared with HC and SLE (P <0.05) and did not correlate with binding to AT-III. - Conclusion: APS anti-FXa IgG have higher avidity to FXa and greater effects upon the enzymatic and coagulant activity of FXa compared with SLE anti-FXa IgG. Further studies of anti-FXa antibodies in APS, SLE and other non-autoimmune thrombotic disease cohorts are now required to evaluate whether targeting FXa with selective inhibitors in patients bearing anti-FXa antibodies may be an effective treatment strategy.

    Metadata

    Item Type: Article
    School: Central Administration Departments > Master's Office
    Depositing User: Administrator
    Date Deposited: 20 Apr 2015 12:56
    Last Modified: 20 Apr 2015 12:56
    URI: http://eprints.bbk.ac.uk/id/eprint/11948

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