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AUTOANTIBODY RELATED DISRUPTION OF KALLIKREIN-KININSYSTEM IN RECURRENT PREGNANCY LOSS

复发性流产中激肽释放酶-激肽系统自身抗体相关破坏

基本信息

批准号：
13671748
负责人：
SUGI Toshitaka
金额：
$ 2.18万
依托单位：
Tokai University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

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

抗磷脂抗体（aPL）在血栓形成、血小板减少症和复发性妊娠丢失（RPL）患者中有报道。我们最近报道了抗磷脂酰乙醇胺抗体（aPE）和RPL之间的强关联（Fertil Steril，71，1060，1999）。我们还报道了某些aPE对磷脂酰乙醇胺（PE）本身不是特异性的，而是针对PE结合血浆蛋白，如激肽原（Blood，86，3083，1995）。凝血因子XII、前激肽释放酶和高分子量激肽原被认为是凝血内源性途径中的血浆接触蛋白。然而，这些蛋白质的缺陷与临床出血无关，尽管体外表面活化凝血时间显着延长。特别的是，研究表明这些蛋白质在生理环境中对内皮细胞具有抗凝血、促纤维蛋白溶解的功能。最近，令人惊讶的高发病率因子XII缺乏症的患者， ...更多信息有复发性血栓形成和RPL的报告。由于已报告狼疮抗凝患者存在因子XII抗体，我们现在检测了RPL患者的血浆样本的因子XII活性、因子XII抗原浓度和因子XII自身抗体的存在。对191例RPL患者进行因子XII活性筛查。我们发现34例（17.8%）患者存在因子XII缺乏（活性<60%）。这34例患者中有18例（52.9%）aPL阳性。我们的数据显示RPL与因子XII缺乏相关（p=0.0028）。我们假设因子XII缺乏可能部分是由于存在因子XII的抗体，并通过免疫印迹和生物分子相互作用分析检测因子XII缺乏患者的血浆样本中存在因子XII的抗体。我们发现，因子XII抗体存在于一个显着的比例因子XII缺乏患者与RPL。少

项目成果

期刊论文数量（75）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

牧野恒久, 杉俊隆: "異常妊娠にかかわる免疫学-免疫学的にみた不妊、不育症"産婦人科の世界. 53. 171-176 (2001)

Tsunehisa Makino，Toshitaka Sugi：“与异常妊娠相关的免疫学 - 从免疫学角度看不孕症和不孕症”《妇产科世界》53. 171-176 (2001)。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

菊池公孝, 村野孝代, 内田能安, 林田研一, 杉俊隆, 森晃, 岩崎克彦, 牧野恒久: "合併症妊娠における人工妊娠中絶"日産婦神奈川会誌. 38. 142-146 (2002)

Kimitaka Kikuchi、Takayo Murano、Yoshiyasu Uchida、Kenichi Hayashida、Toshitaka Sugi、Akira Mori、Katsuhiko Iwasaki、Tsunehisa Makino：“复杂妊娠中的人工流产”日产神奈川妇产科杂志 38. 142-146 (2002)。