TY - JOUR
T1 - Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death
AU - Hurtado, Verónica
AU - Montes, Ramón
AU - Gris, Jean Christophe
AU - Bertolaccini, María L.
AU - Alonso, Álvaro
AU - Martínez-González, Miguel A.
AU - Khamashta, Munther A.
AU - Fukudome, Kenji
AU - Lane, David A.
AU - Hermida, José
PY - 2004/9/1
Y1 - 2004/9/1
N2 - The antiphospholipid syndrome (APS) is associated with thrombosis and fetal death but the pathologic mechanisms are poorly understood. Since endothellal 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.
AB - The antiphospholipid syndrome (APS) is associated with thrombosis and fetal death but the pathologic mechanisms are poorly understood. Since endothellal 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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U2 - 10.1182/blood-2004-03-0793
DO - 10.1182/blood-2004-03-0793
M3 - Article
C2 - 15150078
AN - SCOPUS:4444301246
SN - 0006-4971
VL - 104
SP - 1369
EP - 1374
JO - Blood
JF - Blood
IS - 5
ER -