title: Autoantibodies against endothelial protein C receptor and the risk of a first deep vein thrombosis.
abstract: BACKGROUND
  The endothelial protein C receptor (EPCR) binds protein C and enhances its activation. Anti-EPCR autoantibodies are found in patients with antiphospholipid syndrome and may explain the increased risk of thrombosis in these patients. Anti-EPCR autoantibodies have been associated with fetal death and myocardial infarction in young women.
  
  
  OBJECTIVE
  To determine whether anti-EPCR autoantibodies are associated with deep vein thrombosis (DVT).
  
  
  METHODS
  We measured plasma anti-EPCR autoantibody levels in the Leiden Thrombophilia Study (LETS), a population-based case-control study consisting of 474 patients with a first DVT and 474 control subjects.
  
  
  RESULTS
  The estimated risk of DVT was increased approximately 2-fold in the presence of elevated IgA, IgG or IgM anti-EPCR autoantibodies (i.e. levels above the 90th percentile as measured in the control subjects). The risk conferred by anti-EPCR increased in a dose-dependent manner for IgA and IgG. When anti-EPCR autoantibodies were considered in the co-presence of lupus anticoagulant (LAC) the odds ratio (OR) was 6.1 [95% CI 1.3-27.9]. Anti-EPCR without LAC remained associated with DVT (OR 1.6; 95% CI 1.2-2.1). Anti-EPCR autoantibodies were associated with high levels of D-dimer and soluble EPCR in controls, suggestive of a prothrombotic status induced by the autoantibodies.
  
  
  CONCLUSIONS
  This study demonstrates that the presence of anti-EPCR autoantibodies is a moderate risk factor for DVT in the general population.
authors: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: A
authors: A
authors: van Hylckama Vlieg
authors: R
authors: R
authors: Montes
authors: F R
authors: FR
authors: Rosendaal
authors: J
authors: J
authors: Hermida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D000074283:Endothelial Protein C Receptor; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D016682:Lupus Coagulation Inhibitor / Q000097:blood; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000276:immunology*; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology* / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D000074283:Endothelial Protein C Receptor; D005338:Fibrin Fibrinogen Degradation Products; D016682:Lupus Coagulation Inhibitor; C478370:PROCR protein, human; D011486:Protein C; D011956:Receptors, Cell Surface; C036309:fibrin fragment D