Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death.
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.
Hurtado
Verónica
V
Haematology Department, Clínica Universitaria, University of Navarra, Avenida Pío XII 36, 31008 Pamplona, Spain.
Montes
Ramón
R
Gris
Jean-Christophe
JC
Bertolaccini
María L
ML
Alonso
Alvaro
A
Martínez-González
Miguel A
MA
Khamashta
Munther A
MA
Fukudome
Kenji
K
Lane
David A
DA
Hermida
José
J
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
D015703:Antigens, CD; D001323:Autoantibodies; D000074283:Endothelial Protein C Receptor; D016232:Endothelins; D006023:Glycoproteins; C478370:PROCR protein, human; D011956:Receptors, Cell Surface