Pregnancies complicated with antiphospholipid syndrome: the pathogenic mechanism of antiphospholipid antibodies: a review of the literature.
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.
Di Simone
Nicoletta
N
Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy. nicolettadisimone@rm.unicatt.it
Luigi
Meroni Pier
MP
Marco
D'Asta
D
Fiorella
Di Nicuolo
DN
Silvia
D'Ippolito
D
Clara
D'Alessio Maria
DM
Alessandro
Caruso
C
D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000188:drug therapy / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000209:etiology*; D014327:Trophoblasts / Q000187:drug effects / Q000276:immunology*; D053482:beta 2-Glycoprotein I / Q000276:immunology
D017152:Antibodies, Antiphospholipid; D001324:Autoantigens; D053482:beta 2-Glycoprotein I; D006493:Heparin