Pathogenesis and Prevention of intrauterine growth retardation and fetal distress by antiphospholipid antibody

1.先兆子痫患者血清中存在抗心磷脂抗体(ACA)，抗心磷脂抗体(ACA)与胎盘绒毛结合能力强，在ACA阳性患者中，胎儿宫内生长迟缓(IUGR)发生率较高。2.用β_2-GPI检测ACA阳性孕妇胎盘功能不全和IUGR的发生率较高。3.观察β_2-GPI依赖性ACA对内皮细胞的影响，探讨β_2-GPI依赖性ACA的发病机制。ACA有降低PGF1；α&GT；产量的趋势。而ACA可增加内皮细胞产生的强血管活性物质内皮素-1(ET-1)。从ACA阳性血清中分离出免疫球蛋白G，证明该血清的作用来源于免疫球蛋白，并评价了其对依赖β2-GPI的ACA产生细胞因子的影响。β2-GPI对PGF1α和ET-1的产生有抑制作用。当评价β_2-GPI本身对细胞因子产生的影响时，IL-1的产生有增加的趋势，而IL-6和IL-8没有变化。β_2-GPI依赖的ACA可能通过抑制ET-1的产生而抑制ET-1的产生。提示ACA可能与胎盘绒毛和血管内皮细胞结合，ET-1分泌增加引起的血管收缩可能产生IUGR。

1.We demonstrated the presence of anticardiolipin antibody (ACA) in preeclampsia and the binding ability for placental villi by ACA.In ACA positive cases, high incidence of intrauterine growth retardation (IUGR) was found. 2.Using the ELISA using beta_2-GPI,high incidence of placental insufficiency and IUGR were detected in positive ACA cases. 3.To investigate the pathogenetic mechanism by beta2-GPI dependent ACA,the effects on beta2-GPI dependent ACA for endothelial cell were evaluated. ACA tended to decrease the PGF1_<alpha> production. However, ACA increased the production of Endothelin 1 (ET-1) which is strong vasoactive substance from endothelial cell. After isolation of IgG from ACA positives sera, we demonstrated that the effect of sera was originated from IgG.Moreover, the effects on cytokine production by beta2-GPI dependent ACA was evaluated. The IL8 production tended to increase without the changes of IL1 alpha and IL6.4.When the effect on the productions of PGF1 alpha and ET-1 by beta2-GPI itself was evaluated, beta_2-GPI suppressed those productions. When the effects on the cytokine productions by beta_2-GPI itself were evaluated, the IL1 production tended to increase without the changes of IL6 and IL8. There is a possibility that beta_2-GPI dependent ACA prevents to suppress the production of ET-1.We suggest that ACA may bind to placental villi and endothelium during pregnancy and that the vascular constriction by increased ET-1 production may produce IUGR.