It is widely accepted that the persistent presence of antiphospholipid antibodies (aPL) represents a high risk factor for recurrent spontaneous abortion, fetal growth retardation, and complicated pregnancies (early and severe preeclampsia). However, whether aPL can be regarded as direct pathogenetic antibodies and which pathogenetic mechanism sustains the clinical manifestations are still open questions. We approached the problem by (a) setting up an experimental model of fatal loss in naive mice; and (b) by investigating the deposition of β2 glycoprotein I (β2 GPI)-the plasma cofactor for aPL-on placentae from women suffering from aPL-associated recurrent abortion. In the experimental model we found that intravenous injection of 10 μg of different aPL preparations in BALB/c mice after mating reduced the fecundity, increased the number of resorptions, and reduced the embryos and the placental weights in comparison with mice treated with control immunoglobulins. Altogether these findings support the direct pathogenetic role for aPL. Interestingly, aPL-treated mice displayed widespread thrombotic manifestations on the maternal side of the placentae, suggesting that placental thrombosis could be one of the pathogenetic events in aPL-associated fetal loss as previously hypothesized from occasional histological observations in human studies. The fact that aPL do really play a role in recurrent fatal loss is also supported by our immunohistological studies on placentae from women with aPL-associated fetal loss. In fact, we found an increased deposition of β2 GPI-the plasma cofactor for aPL antibodies-on the trophoblast and endothelial surfaces. A comparable immunoglobulin G (IgG) deposition on the same structures was also found. We suggest that β2 GPI can bind to negatively charged phospholipids exposed during trophoblast syncitium formation, so offering an immunogenic epitope for circulating aPL. The immune complex might in turn alter trophoblast function or could simply reduce the available amount of natural circulating anticoagulant (named β2 GPI).
|Original language||English (US)|
|Number of pages||6|
|State||Published - Jan 1 1995|
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