抗リン脂質抗体症候群における母児相関 : 免疫学的血液凝固異常を中心に (<シンポジウム>2. 母児間免疫応答の異常)

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Antiphospholipid antibodies (aPA) to anionic phospholipids such as cardiolipin and phosphatidylserine have been described in patients with thrombosis, thrombocytopenia and recurrent fetal loss. Autoantibodies reactive to zwitterionic phospholipids such as phosphatidylethanolamine (PE) have not been studied extensively. Most lupus anticoagulatnt and aPA literature is limited to descriptions of anionic phospholipids such as cardiolipin, however, antiphosphatidylethanolamine antibodies (aPE ) also have been described in patients with thrombotic diseases. Since PE is a major component of both the outer and inner leaflet of cell plasma membranes, production of aPE may interfere with normal cell functions. We reported that certain aPE are not specific for PE per se, but are directed to PE-binding plasma proteins, kininogens. Many aPE recognize a kininogen-PE complex and neither PE nor kininogen when they are presented independently. We showed a strong association between recurrent pregnancy loss and aPE, the latter of which requires the presence of kininogen or other plasma proteins. Our data suggest that aPE may represent a significant risk factor for early recurrent pregnancy loss. The kallikrein-kinin system or plasma contact system consists of three essential plasma proteins that interact upon binding to negatively charged surfaces. These are coagulation factor XII, prekallikrein, and high molecular weight kininogen. Deficiencies of these proteins are not associated with clinical bleeding despite marked prolonged activated partial thromboplastin time (aPTT), a surface-activated coagulation protein screening test. Paradoxically, studies suggest that contact proteins have anticoagulant, profibrinolytic functions in a physiologic milieu, on endothelial cells. Evidence for the presence of the kallikrein-kinin system in fetoplacental vessels has accumulated in several studies. Kinins could influence placental blood flow regulation and have anti-thrombotic/profibrinolytic activities. It was concluded that kinins are released within the placenta and may play a role in regulating placental blood flow and transplacental transport of substrates and metabolites. Recently, numerous studies have suggested an association between contact protein deficiencies and recurrent pregnancy loss, and between autoantibodies to contact proteins and recurrent pregnancy loss. We reported a strong association between recurrent pregnancy loss and aPE, the latter of which requires the presence of kininogen. Also, a surprisingly high prevalence of factor XII deficiency among patients with recurrent thrombosis has been reported. Recently, the presence of antibodies to factor XII in patients with aPA has been reported. Since contact proteins may play an important role in pregnancy especially in fetoplacental unit, deficiencies of these proteins and / or autoantibodies to these proteins may be associated with pregnancy losses. Disruption of this system may be a risk factor for early gestational loss.
社団法人日本産科婦人科学会の論文
1999-08-01

抗リン脂質抗体症候群における母児相関 : 免疫学的血液凝固異常を中心に (<シンポジウム>2. 母児間免疫応答の異常)

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