Sulfatides: targets for anti-phospholipid antibodies.
Sulfatides: targets for anti-phospholipid antibodies.
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脑硫脂：抗磷脂抗体的靶标。
DOI：
10.1161/01.cir.0000095030.44185.6a
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Thiagarajan,P
中科院分区：
文献类型：
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作者：
Merten,M;Motamedy,S;Ramamurthy,S;Arnett,FC;Thiagarajan,P
背景-硫酸脂是表达于红细胞、白细胞和血小板表面的硫酸化鞘糖脂。硫酸脂与几种参与止血的细胞粘附分子相互作用。β2-糖蛋白I是一种阴离子磷脂结合血浆蛋白，磷脂结合形式是大多数抗磷脂抗体的靶标，这些抗体与复发性血栓形成、流产和神经系统症状相关。在这项研究中，我们研究了β2-糖蛋白I是否与硫苷脂形成复合物，从而成为抗磷脂抗体的靶点。方法和结果-β2-糖蛋白I与表面结合的硫苷脂结合，但不与其他糖脂结合，如神经酰胺、神经糖苷、鞘磷脂或神经节苷脂。在1 μg/孔的硫苷脂包被密度下，β2-糖蛋白I在2.5 μg/mL时达到半最大结合，在10 μg/mL时结合饱和。β2-糖蛋白I的结合也取决于孔中硫苷脂的包被密度。在5 μg/mL的恒定β2-糖蛋白I浓度下，在1 μg/孔的包被密度下观察到β2-糖蛋白I的最大结合。来自14名具有抗心磷脂抗体（抗磷脂抗体的一个子集）的患者的血清与硫酸脂结合的β2-糖蛋白I结合，并且先前在心磷脂包被的表面上吸收，在14名患者中的12名患者中，对硫苷脂-β2-糖蛋白I复合物的免疫反应性降低>50%。此外，免疫亲和纯化的抗心磷脂抗体与硫酸脂结合的β2-糖蛋白I的反应，从5例中的4例。结论这些结果表明，不仅阴离子磷脂，众所周知，但也硫酸脂是大多数抗磷脂抗体的目标。因此，我们推测这些抗体与硫苷脂的相互作用可能导致抗磷脂抗体综合征的一些临床症状。
Background—Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. β2-Glycoprotein I is an anionic phospholipid-binding plasma protein, and the phospholipid-bound form is the target for most anti-phospholipid antibodies that are associated with recurrent thrombosis, miscarriages, and neurological symptoms. In this study, we examined whether β2-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies.Methods and Results—β2-Glycoprotein I binds to surface-bound sulfatides but not to other glycolipids, such as ceramide, cerebrosides, sphingomyelin, or ganglioside. At a sulfatide coating density of 1 μg/well, β2-glycoprotein I reaches half-maximal binding at 2.5 μg/mL, and the binding is saturated at 10 μg/mL. The binding of β2-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant β2-glycoprotein I concentration of 5 μg/mL, maximal binding of β2-glycoprotein I is observed at a coating density of 1 μg/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound β2-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-β2-glycoprotein I complex by >50% in 12 of 14 patients. Furthermore, immunoaffinity-purified anti-cardiolipin antibodies from 4 of 5 patients reacted with sulfatide-bound β2-glycoprotein I.Conclusions—These results show that not only anionic phospholipids, as commonly known, but also sulfatides are targets for most anti-phospholipid antibodies. We therefore postulate that interactions of these antibodies with sulfatides may contribute to some of the clinical symptoms of the anti-phospholipid antibody syndrome.