Antiphospholipid antibodies and pregnancy loss: a disorder of inflammation

Abstract

The antiphospholipid syndrome (APS) is a leading cause of miscarriage and maternal and fetal morbidity. APS is characterized by thrombosis and pregnancy loss that occur in the presence of antiphospholipid (aPL) antibodies. Using a mouse model of APS induced by passive transfer of human aPL antibodies, we have shown that complement activation plays an essential and causative role in pregnancy loss and fetal growth restriction, and that blocking activation of the complement cascade rescues pregnancies. Conventional treatment for APS patients is sub-anticoagulant doses of heparin throughout pregnancy. Could heparin prevent pregnancy loss by inhibiting complement? In our experimental model of APS, heparin inhibits activation of complement on trophoblasts in vivo and in vitro, and anticoagulation in and of itself is not sufficient to prevent pregnancy complications. These studies underscore the importance of inflammation in fetal injury associated with aPL antibodies and raise the importance of developing and testing targeted complement inhibitory therapy for patients with APS.

Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study

“…The results of studies in mouse models suggest that obstetrical APS may be a nonthrombogenic syndrome, [34][35][36][37] but mechanisms of pregnancy loss involving thrombosis have been described recently [36][37][38] and this agrees with our observational results, at least in a subset of patients. LDA-mediated primary prophylaxis was well tolerated in our purely obstetric APS patients, which might have limited the numbers of subsequent thrombotic events.…”

Complement inhibitory proteins expression in placentas of thrombophilic women

“…A strong expression of these proteins on trophoblast surface activates the mechanisms protecting the fe- tus from maternal immunological response [14,15]. Hill et al (1995) did not find any differences in DAF and MCP expression in the placentas of women with recurrent pregnancy losses in the first trimester compared to healthy fertile women [16].…”

Predictors of Pregnancy Outcome in Antiphospholipid Syndrome: A Review

“…Actually, there is emerging evidence that the complement pathway may mediate the inflammatory fetal damage in APS in animal models [36][37][38].…”