AUTOANTIBODY RELATED DISRUPTION OF KALLIKREIN-KININSYSTEM IN RECURRENT PREGNANCY LOSS

抗磷脂抗体(APL)已被描述为血栓形成、血小板减少和复发性妊娠丢失(RPL)的患者。我们最近报道了抗磷脂酰乙醇胺抗体(APE)和RPL之间的强烈关联(Fertil Steril，71,1060,1999)。我们还报道，某些类人猿本身并不是磷脂酰乙醇胺(PE)所特有的，而是针对与PE结合的血浆蛋白，如激肽原(布拉德，86,3083,1995)。凝血因子XII、前激肽释放酶和高分子量激肽原是凝血内在途径中的血浆接触蛋白。然而，这些蛋白的缺乏与临床出血无关，尽管体外表面激活的凝血时间显著延长。矛盾的是，研究表明，这些蛋白质在生理环境中对内皮细胞具有抗凝、纤溶功能。最近，…患者中凝血因子XII缺乏症的患病率高得惊人有更多的TS复发血栓和RPL的报道。自从狼疮抗凝剂患者中存在凝血因子XII抗体的报道以来，我们现在检测了RPL患者的血浆样本中凝血因子XII活性、凝血因子XII抗原浓度以及凝血因子XII自身抗体的存在。对191例慢性阻塞性肺疾病患者进行了凝血因子XII活性筛选。我们发现34例(17.8%)患者存在凝血因子XII缺乏(活动度为60%)。34例中APL阳性18例(52.9%)。我们的数据显示RPL与凝血因子XII缺乏有关(p=0.0028)。我们推测凝血因子XII缺乏的部分原因可能是凝血因子XII抗体的存在，并通过免疫印迹和生物分子相互作用分析检测了凝血因子XII缺乏症患者的血浆样本。我们发现凝血因子XII抗体存在于极大比例的凝血因子XII缺乏的RPL患者中。较少

Antiphospholipid antibodies (aPL) have been described in patients with thrombosis, thrombocytopenia, and recurrent pregnancy loss (RPL). We recently reported that a strong association between antiphosphatidylethanolamine antibodies (aPE) and RPL (Fertil Steril, 71, 1060, 1999). We also reported that certain aPE are not specific for phosphatidylethanolamine (PE) per se but are directed to PE-binding plasma proteins, such as kininogens (Blood, 86, 3083, 1995). Coagulation factor XII, prekallikrein and high molecular weight kininogen are known as plasma contact proteins in the intrinsic pathway of blood coagulation. However, deficiencies of these proteins are not associated with clinical bleeding despite marked prolongation of in vitro surface-activated coagulation time. Paradoxically, studies suggest that these proteins have anticoagulant, profibrinolytic functions in a physiologic milieu, on endothelial cells. Recently, surprisingly high prevalences of factor XII deficiency among patien … More ts with recurrent thrombosis and RPL have been reported. Since the presence of antibodies to factor XII in patients with lupus anticoagulant has been reported, we have now tested plasma samples from RPL patients for the factor XII activity, concentration of factor XII antigen and for the presence of autoantibodies to factor XII. One hundred ninety one patients with RPL were screened for factor XII activity. We found 34 (17.8%) patients with factor XII deficiency (activity<60%). Eighteen (52.9%) of these 34 patients were positive for aPL. Our data show that RPL are associated with factor XII deficiency (p=0.0028). We hypothesized that factor XII deficiency may be partly due to presence of antibodies to factor XII and tested plasma samples from patients with factor XII deficiency for the presence of antibodies to factor XII by immunoblot and biomolecular interaction analysis. We found that factor XII antibodies were present in a significant proportion of factor XII deficient patients with RPL. Less