TY - JOUR
T1 - Pregnancies complicated with antiphospholipid syndrome: the pathogenic mechanism of antiphospholipid antibodies: a review of the literature
AU - Di Simone, Nicoletta
AU - Luigi, Meroni Pier
AU - D'Asta, Marco
AU - Di Nicuolo, Fiorella
AU - D'Ippolito, Silvia
AU - D'Alessio, Maria Clara
AU - Caruso, Alessandro
PY - 2007
Y1 - 2007
N2 - There are several possible mechanisms by which antiphospholipid antibodies (aPL) may have adverse effects on placental functions. Examination of placentas and first-trimester decidua from antiphospholipid syndrome-complicated pregnancies has found little evidence of specific thrombotic placental pathology. It is now generally accepted that the clinically relevant aPL bind to proteins with affinity for phospholipids. The most important epitope for antiphospholipid syndrome-related aPL resides on beta2-glycoprotein-I (beta2GPI). aPL detected by anti-beta2GPI assays are associated with fetal loss. During differentiation to syncytium, trophoblasts express cell membrane anionic phospholipids that can bind beta2GPI. Adhered beta2GPI can be recognized by the antibodies that, once bound, interfere with trophoblast cell maturation, resulting in defective placentation. The improved outcome of pregnancies treated with heparin stimulated interest on the drug's mechanism of action. Several mechanisms could explain its beneficial effects in addition to a direct effect of heparin on the coagulation cascade. It might reduce the binding of aPL, inflammation by inhibiting complement activation, and might facilitate implantation. Further investigations are needed to better understand how aPL induce obstetric complications and to better clarify the functional role of heparin in the human placenta, leading to more successful therapeutic options
AB - There are several possible mechanisms by which antiphospholipid antibodies (aPL) may have adverse effects on placental functions. Examination of placentas and first-trimester decidua from antiphospholipid syndrome-complicated pregnancies has found little evidence of specific thrombotic placental pathology. It is now generally accepted that the clinically relevant aPL bind to proteins with affinity for phospholipids. The most important epitope for antiphospholipid syndrome-related aPL resides on beta2-glycoprotein-I (beta2GPI). aPL detected by anti-beta2GPI assays are associated with fetal loss. During differentiation to syncytium, trophoblasts express cell membrane anionic phospholipids that can bind beta2GPI. Adhered beta2GPI can be recognized by the antibodies that, once bound, interfere with trophoblast cell maturation, resulting in defective placentation. The improved outcome of pregnancies treated with heparin stimulated interest on the drug's mechanism of action. Several mechanisms could explain its beneficial effects in addition to a direct effect of heparin on the coagulation cascade. It might reduce the binding of aPL, inflammation by inhibiting complement activation, and might facilitate implantation. Further investigations are needed to better understand how aPL induce obstetric complications and to better clarify the functional role of heparin in the human placenta, leading to more successful therapeutic options
KW - Antiphospholipid Antibodies
KW - Antiphospholipid Syndrome
KW - Endothelial cells
KW - trophoblast
KW - Antiphospholipid Antibodies
KW - Antiphospholipid Syndrome
KW - Endothelial cells
KW - trophoblast
UR - http://hdl.handle.net/10807/21224
U2 - 10.1196/annals.1422.054
DO - 10.1196/annals.1422.054
M3 - Article
SN - 0077-8923
VL - 1108
SP - 505
EP - 514
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -