title: Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death.
abstract: 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.
authors.affiliation: Haematology Department, Clínica Universitaria, University of Navarra, Avenida Pío XII 36, 31008 Pamplona, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Hurtado
authors.forename: Ramón
authors.initials: R
authors.lastname: Montes
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Gris
authors.forename: María L
authors.initials: ML
authors.lastname: Bertolaccini
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martínez-González
authors.forename: Munther A
authors.initials: MA
authors.lastname: Khamashta
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukudome
authors.forename: David A
authors.initials: DA
authors.lastname: Lane
authors.forename: José
authors.initials: J
authors.lastname: Hermida
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D016736:Antiphospholipid Syndrome / Q000453:epidemiology / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D000074283:Endothelial Protein C Receptor; D016232:Endothelins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005313:Fetal Death / Q000453:epidemiology / Q000276:immunology*; D006023:Glycoproteins; D006801:Humans; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology / Q000276:immunology*; D011956:Receptors, Cell Surface; D012307:Risk Factors
chemical_list: D015703:Antigens, CD; D001323:Autoantibodies; D000074283:Endothelial Protein C Receptor; D016232:Endothelins; D006023:Glycoproteins; C478370:PROCR protein, human; D011956:Receptors, Cell Surface