β2-glycoprotein I gene deficiency (β2GPI-Sapporo) and the progression of atherosclerosis

最近的证据表明，抗磷脂抗体可能有助于动脉粥样硬化病变的形成。在小于45岁的SLE患者中，心肌梗死已被认为是死亡的主要原因。我曾报道，在抗磷脂综合征（APS）患者中发现的aCL不是简单地指向CL结构，而是需要β2-糖蛋白I （β2GPI）的存在才能结合，并且当β2GPI与氧取代的固体表面相互作用时，表位通过发生构象变化来表达。Β2GPI特异性结合血液中的氧化LDL和氧化脂蛋白，特别是氧化LDL，也被Β2GPI和aCL顺序靶向，该免疫反应不仅参与血浆脂蛋白的代谢，还参与APS伴动脉粥样硬化事件的血栓性并发症。采用夹心EIA法测定了812例明显健康的日本人血清β 2gpi浓度。鉴定出2个完全β 2gpi缺乏症家族。在每个β2GPI缺陷个体中，缺失了与β2GPI cDNA 379位对应的胸腺嘧啶。RFLP测定的这种杂合缺乏症在日本人中的发生率为6.3%，而在高加索人中，杂合子的血清β 2gpi浓度没有显著低于没有突变的人，但血脂谱，如总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、apoA-I、载脂蛋白ob和脂蛋白(a)没有明显差异。低浓度的β 2gpi似乎与脂蛋白代谢的明显异常无关。

Recent evidence suggested that antiphospholipid antibodies may have contributed to the formation of atherosclerotic lesions. In SLE less than 45 years of age, myocardial infarction has been recognized as a major cause of mortality. I have reported that aCL found in patients with antiphospholipid syndrome (APS) are not simply directed to the CL structure, but require the presence of β2-glycoprotein I (β2GPI) for bindng and that the epitopes is expressed by conformational changes occurring whenβ2GPI interacts with an oxygen-substituted solid surface. Β2GPI specifically bound to oxidized LDL and oxidized lipoproteins in the blood, especially oxidized LDL, are also sequentially targeted by β2GPI and aCL, and that immunoreaction is involved not only in the metabolism of plasma lipoproteins but also in thrombotic complications accompanied by atherosclerotic events in APS.Serumβ2GPI concentration of 812 apparently healthy Japanese individuals was measured by sandwich EIA. Two families with completeβ2GPI deficiency were identified. A thymine corresponding to position 379 of the β2GPI cDNA was deleted in every β2GPI deficient individual. The incidence of this heterozygous deficiency determined by RFLP was 6.3% in Japanese and none in Caucasians Heterozygotes had significantly lower concentrations of serumβ2GPI than did those without the mutation, yet no significantly different lipid profiles, such as total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, apoA-I, apoB and Lp(a), were observed. A low concentration ofβ2GPI seemed not to be associated with apparent abnormality in lipoprotein metabolism.