Human Reproduction Update Advance Access originally published online on November 11, 2006
Human Reproduction Update 2007 13(2):189-196; doi:10.1093/humupd/dml051
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Pathogenic role of anti-ß2-glycoprotein I antibodies on human placenta: functional effects related to implantation and roles of heparin
1 Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome and 2 Allergy, Clinical Immunology and Rheumatology Unit, IRCCS, Istituto Auxologico Italiano, Milan, Italy
3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Largo Gemelli 8, 00168 Rome, Italy. E-mail: nicolettadisimone{at}rm.unicatt.it
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Abstract |
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Most of the clinical manifestations of the antiphospholipid syndrome (APS) can be related to thrombotic events; however, placental thrombosis cannot explain all of the pregnancy complications that occur in women with this syndrome. In this regard, it has been hypothesized that antiphospholipid (aPL) antibodies can directly attack trophoblasts, but it is still unclear what pathogenetic mechanisms play a role and which aPL antibodies subpopulations are involved. Although it has been assumed that aPL antibodies are directed against anionic phospholipids (PLs), current advances in the field suggest that antibodies to PL-binding plasma protein such as ß2-glycoprotein-I (ß2-GPI) are the clinically relevant aPL antibodies. It appears that following the attachment of ß2-GPI to PLs, both molecules undergo conformational changes that result in the exposure of cryptic epitopes within the structure of ß2-GPI allowing the subsequent binding of antibodies. aPL antibodies detected by anti-ß2-GPI assays are associated with fetal loss. However, there is still debate on how the antibodies might induce the obstetrical manifestations. The significantly improved outcome of pregnancies treated with heparin has stimulated interest in the drug’s mechanisms of action. Several mechanisms could explain its beneficial effects, because in addition to a direct effect of heparin on the coagulation cascade, it might protect pregnancies by reducing the binding of aPL antibodies, reducing inflammation, facilitating implantation and/or inhibiting complement activation. Further investigations are needed to better understand how aPL antibodies induce obstetric complications and to better clarify the functional role of heparin in the human placenta leading to more successful therapeutic options.
Key words: placenta / antiphospholipid syndrome / ß2-glycoprotein I / heparin / antiphospholipid antibodies
Received on July 13, 2006; revised September 18, 2006; accepted on October 9, 2006