Updating on the Pathogenic Mechanisms 5 of the Antiphospholipid Antibodies-Associated Pregnancy Loss

Abstract

Anti-phospholipid antibodies (aPL) are risk factor for recurrent pregnancy loss and obstetrical complications. The mechanisms of aPL-mediated pregnancy failure are still a matter of research. Although aPL are associated with thrombosis, thrombotic events cannot explain all the miscarriages. There is evidence for a direct in vitro aPL effect on the trophoblast as shown by their binding; reduction of proliferation, human chorionic gonadotrophin release, in vitro invasiveness, adhesion molecule expression; and increased apoptosis. Such a direct reactivity is supported by the expression of beta2 glycoprotein (beta 2GP) I on trophoblast cell membranes. aPL/anti-beta 2GPI antibodies also bind to human decidual/endometrial cells in vitro and induce a pro-inflammatory phenotype. APL-mediated inflammatory processes at the placental level are apparently responsible for fetal loss at least in animal models. Both complement activation and pro-inflammatory cytokine/chemokine secretion have been shown to play a role. More recently, complement-induced tissue factor expression on infiltrating neutrophils was described as an additional pathogenic mechanisms mediated by aPL. As a whole, these findings do suggest that aPL may induce a defective placentation by acting at different levels without involving necessarily thrombotic events.

Association between the Presence of Serumanti-Cardiolipin Antibodies and Infertility

“…While, secondary infertility is difficulty conceiving after already having conceived. In spite of the bulk knowledge about APA, the concept of autoimmune basis of infertility is still controversial, particularly regarding the presence of ACL [10] [11] [18]. In the present study, the significantly higher ACL IgM positivity rate in women with primary infertility was consistent with that reported by other workers [12] [14].…”

“…The concept of autoimmune basis of infertility is still controversial, particularly regarding the presence of ACL [10] [11]. It has been found that in fertile women, ACL was below the negative cut-off value, while women with unexplained infertility were positive in 23.8%.…”

Pravastatin improves pregnancy outcomes in obstetric antiphospholipid syndrome refractory to antithrombotic therapy

“…Pregnancy complications in APS (recurrent unexplained abortions, spontaneous fetal loss, preeclampsia [PE], and premature birth) have been attributed to placental thrombosis and infarcts, and management of these patients is based on attenuating the procoagulant state. However, in many cases, there is no evidence of decidual thrombosis or placental vasculopathy, and instead, inflammatory signs are present (2)(3)(4). Treatment with low-dose aspirin (LDA) and heparinoids has become a conventional option for pregnant women with APS.…”

Antiphospholipid antibodies induce translocation of TLR7 and TLR8 to the endosome in human monocytes and plasmacytoid dendritic cells

“…3 The pathogenetic role of aPL has been well established in various animal models of thrombosis and pregnancy. 1,4,5 Furthermore, several potentially procoagulant properties of aPLs have been described in cell culture models, the most prominent being their ability to induce inappropriate expression of tissue factor in monocytes and endothelial cells. 6 However, the underlying signal transduction is still not fully understood.…”