Detection of antitrophoblast antibodies in the sera of patients with anticardiolipin antibodies and fetal loss

Abstract

Women with anticardiolipin antibodies (ACLA) are at increased risk for fetal loss. One potential explanation for this outcome is that sera from these individuals contain antibodies reactive with trophoblast cells, which are involved in the establishment of the uteroplacental vasculature and maintenance of placental blood fluidity. To examine this hypothesis, we compared the incidence of trophoblast-reactive antibodies in 27 patients with ACLA and a history of fetal loss with that in 29 normal pregnant women. Sera from 20 patients, but only one control, contained trophoblast-reactive antibodies (P < .001). These antibodies were not directed against major histocompatibility class I antigens, and reacted with both term and first-trimester trophoblast cells. In most cases, sera from which ACLA were adsorbed by cardiolipin- containing liposomes maintained reactivity against cells. In addition, patient Ig fractions immunoprecipitated an approximately 62-kD protein from the trophoblast cell surface, stimulated the release of arachidonic acid and thromboxane A2 by trophoblasts, and inhibited the binding of prourokinase to trophoblast urokinase receptors. These observations show that sera from women with ACLA and a history of fetal loss contain antitrophoblast antibodies. These antibodies may be serologically distinct from ACLA, and may contribute to the pathogenesis of fetal demise.

Placentation, antiphospholipid syndrome and pregnancy outcome

“…Although derived from measurement of cell proliferation in choriocarcinoma cell-lines (Jar and BeWo) exposed to aPL, this study provides strong supportive evidence for the decidual vasculopathỳ theory' of APS pregnancies. Others 69 have suggested the presence of antitrophoblast antibodies in APS pregnancies. Another recent study demonstrated reduced prolactin and insulin-like growth factor binding protein-1 expression in an in vitro model of endometrial stromal cell decidualization, suggesting that aPLs interfere with endometrial differentiation and that this may contribute to the incomplete formation of a functional feto-maternal interface.…”

The effects of antiphospholipid antibodies obtained from women with SLE/APS and associated pregnancy loss on rat embryos and placental explants in culture

“…Other investigators have demonstrated the presence of antitrophoblast antibodies in APS patients with fetal loss. 13 They may impair the fusion of cytotrophoblastic cells in vitro to form syncytial cells, which is a critical step in the development and maturation of the villous trophoblast. 14 Following these and our previous studies demonstrating yolk sac damage caused in cultured rat embryos by serum from women with SLE/APS and RPL, we hypothesized that sera from these same patients would adversely affect the development of the placenta in culture.…”

Síndrome do anticorpo antifosfolípide: estudo comparativo das formas primária e secundária

“…Os achados histopatológicos típicos em placentas de mães com SAF são trombose placentária e infarto. Entretanto, em muitos casos de perda gestacional, especialmente em abortamento espontâneo, não há evidências de trombose placentária, podendo haver outros mecanismos envolvidos na perda gestacional da SAF, como: alterações na secreção placentária de gonadotrofina coriônica humana (21) , reatividade cruzada dos anticorpos antifosfolípides com fosfolípides trofoblásticos e conseqüente exposição das vilosidades trofoblásticas à destruição por células maternas imunoefetoras (22) e redução dos níveis séricos de interleucina-3 induzida pelo anticorpo anticardiolipina (23) .…”