title: Anti-factor Xa antibodies in patients with antiphospholipid syndrome and their effects upon coagulation assays.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Rheumatology Research, Rayne Institute, University College London, London, UK. bahartimesen@gmail.com.|Division of Rheumatology, Department of Internal Medicine, Istanbul Faculty of Medicine, Istanbul University, 34098 Çapa, Fatih, Istanbul, Turkey. bahartimesen@gmail.com.
authors.forename: Bahar
authors.initials: B
authors.lastname: Artim-Esen
authors.affiliation: Centre for Rheumatology Research, Rayne Institute, University College London, London, UK. c.pericleous@ucl.ac.uk.
authors.forename: Charis
authors.initials: C
authors.lastname: Pericleous
authors.affiliation: Haemostasis Research Unit, Department of Haematology, University College London, London, UK. i.mackie@ucl.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Mackie
authors.affiliation: Centre for Rheumatology Research, Rayne Institute, University College London, London, UK. v.ripoll-nunez@ucl.ac.uk.
authors.forename: Vera M
authors.initials: VM
authors.lastname: Ripoll
authors.affiliation: Birkbeck, University of London, Malet Street, London, WC1E 6JF, USA. master@bbk.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Latchman
authors.affiliation: Centre for Rheumatology Research, Rayne Institute, University College London, London, UK. d.isenberg@ucl.ac.uk.
authors.forename: David
authors.initials: D
authors.lastname: Isenberg
authors.affiliation: Centre for Rheumatology Research, Rayne Institute, University College London, London, UK. anisur.rahman@ucl.ac.uk.
authors.forename: Anisur
authors.initials: A
authors.lastname: Rahman
authors.affiliation: Arthritis Research UK Centre for Adolescent Rheumatology, University College London, UCL Hospital and Great Ormond Street Hospital, London, UK. y.ioannou@ucl.ac.uk.
authors.forename: Yiannis
authors.initials: Y
authors.lastname: Ioannou
authors.affiliation: Centre for Rheumatology Research, Rayne Institute, University College London, London, UK. i.giles@ucl.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Giles
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001777:Blood Coagulation; D004797:Enzyme-Linked Immunosorbent Assay; D015951:Factor Xa / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D001323:Autoantibodies; D015951:Factor Xa