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Blood, 1 September 2004, Vol. 104, No. 5, pp. 1369-1374.
Prepublished online as a Blood First Edition Paper on May 18, 2004; DOI 10.1182/blood-2004-03-0793.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death
Verónica Hurtado,
Ramón Montes,
Jean-Christophe Gris,
María L. Bertolaccini,
Álvaro Alonso,
Miguel A. Martínez-González,
Munther A. Khamashta,
Kenji Fukudome,
David A. Lane, and
José Hermida
From the Haematology Department and the Division of Cardiovascular Pathophysiology, Laboratory of Thrombosis and Haemostasis, Clínica Universitaria/School of Medicine, Applied Medical Research Centre, University of Navarra, Pamplona, Spain; Haematology Laboratory, University Hospital, Nîmes, France; Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, London, United Kingdom; Department of Epidemiology and Public Health, School of Medicine, University of Navarra, Pamplona, Spain; Department of Immunology, Saga Medical School, Saga, Japan; and Department of Haematology–Division of Investigative Science, Hammersmith Campus, Imperial College, London, United Kingdom.
The antiphospholipid syndrome (APS) is associated with thrombosis and fetal death but the pathologic mechanisms are poorly understood. Since endothelial protein C receptor (EPCR) plays a role in the anticoagulant system and in placental development, we hypothesized that anti-EPCR autoantibodies may be involved in clinical manifestations of APS and in fetal loss. The levels of immunoglobulin M (IgM) and IgG anti-EPCR autoantibodies were analyzed by enzyme-linked immunosorbent assay (ELISA) in 43 patients with APS and 43 controls. Anti-EPCR levels were higher in APS patients than in controls. Interestingly, one of the IgM anti-EPCR autoantibodies inhibited the generation of activated protein C on endothelium. Since markedly high anti-EPCR levels were found in women with fetal death, 87 patients with a first episode of unexplained fetal death were subsequently analyzed and their anti-EPCR levels were compared with 87 matched controls. We found that anti-EPCR autoantibodies constitute an independent risk factor for a first fetal death episode: the adjusted odds ratios (ORs) for anti-EPCR autoantibodies above the 95th percentile were 23.0 (95% confidence interval [CI], 2.0-266.3) for IgM and 6.8 (95% CI, 1.2-38.4) for IgG. Anti-EPCR autoantibodies can be detected in APS patients and are independent risk factors for fetal death.
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