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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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Submitted March 2, 2004
Accepted April 29, 2004
Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for foetal death
Veronica Hurtado, Ramon Montes, Jean-Christophe Gris, Maria L Bertolaccini, Alvaro Alonso, Miguel A Martinez-Gonzalez, Munther A Khamashta, Kenji Fukudome, David A Lane, and Jose Hermida*
Haematology Department and Division of Cardiovascular Pathophysiology, Laboratory of Thrombosis and Haemostasis, Clinica Universitaria / School of Medicine. Foundation for Applied Medical Research. University of Navarra, Pamplona, Spain
Haematology Laboratory, University Hospital, Nimes, 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
Department of Haematology-Division of Investigative Science, Hammersmith Campus, Imperial College, London, United Kingdom
* Corresponding author; email: jhermida{at}unav.es.
The antiphospholipid syndrome (APS) is associated with thrombosis and foetal death but the pathological mechanisms are poorly understood. Since endothelial protein C receptor (EPCR) plays a role in the anticoagulant system and in placental development, we hypothesised that anti-EPCR autoantibodies may be involved in clinical manifestations of APS and in foetal loss. The levels of IgM and IgG anti-EPCR autoantibodies were analysed by 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 foetal death, 87 patients with a first episode of unexplained foetal death were subsequently analysed and their anti-EPCR levels compared with 87 matched controls. We found that anti-EPCR autoantibodies constitute an independent risk factor for a first foetal death episode: the adjusted odds ratios (OR) 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 foetal death.
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