Abstract
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 β2-glycoprotein-I (β2GPI). aPL detected by anti-β2GPI assays are associated with fetal loss. During differentiation to syncytium, trophoblasts express cellmembrane anionic phospholipids that can bind β2GPI. Adhered β2GPI 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.
| Original language | English |
|---|---|
| Title of host publication | Annals of the New York Academy of Sciences |
| Pages | 505-514 |
| Number of pages | 10 |
| Volume | 1108 |
| DOIs | |
| Publication status | Published - Jun 2007 |
Publication series
| Name | Annals of the New York Academy of Sciences |
|---|---|
| Volume | 1108 |
| ISSN (Print) | 00778923 |
| ISSN (Electronic) | 17496632 |
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Keywords
- Anti-β2-glycoprotein-I
- Antiphospholipid syndrome
- Heparin
- Trophoblast cells
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Pregnancies complicated with antiphospholipid syndrome : The pathogenic mechanism of antiphospholipid antibodies. A review of the literature. / Di Simone, Nicoletta; Luigi, Meroni Pier; Marco, D'Asta; Fiorella, Di Nicuolo; Silvia, D'Ippolito; Clara, D'Alessio Maria; Alessandro, Caruso.
Annals of the New York Academy of Sciences. Vol. 1108 2007. p. 505-514 (Annals of the New York Academy of Sciences; Vol. 1108).Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - Pregnancies complicated with antiphospholipid syndrome
T2 - The pathogenic mechanism of antiphospholipid antibodies. A review of the literature
AU - Di Simone, Nicoletta
AU - Luigi, Meroni Pier
AU - Marco, D'Asta
AU - Fiorella, Di Nicuolo
AU - Silvia, D'Ippolito
AU - Clara, D'Alessio Maria
AU - Alessandro, Caruso
PY - 2007/6
Y1 - 2007/6
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 β2-glycoprotein-I (β2GPI). aPL detected by anti-β2GPI assays are associated with fetal loss. During differentiation to syncytium, trophoblasts express cellmembrane anionic phospholipids that can bind β2GPI. Adhered β2GPI 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 β2-glycoprotein-I (β2GPI). aPL detected by anti-β2GPI assays are associated with fetal loss. During differentiation to syncytium, trophoblasts express cellmembrane anionic phospholipids that can bind β2GPI. Adhered β2GPI 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 - Anti-β2-glycoprotein-I
KW - Antiphospholipid syndrome
KW - Heparin
KW - Trophoblast cells
UR - http://www.scopus.com/inward/record.url?scp=34948886689&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34948886689&partnerID=8YFLogxK
U2 - 10.1196/annals.1422.054
DO - 10.1196/annals.1422.054
M3 - Conference contribution
C2 - 17894016
AN - SCOPUS:34948886689
SN - 157331708X
SN - 9781573317085
VL - 1108
T3 - Annals of the New York Academy of Sciences
SP - 505
EP - 514
BT - Annals of the New York Academy of Sciences
ER -