Sulfatides - Targets for anti-phospholipid antibodies

Article

关键词: AMINO-ACID-SEQUENCE;    BETA-2-GLYCOPROTEIN-I APOLIPOPROTEIN-H;    LUPUS ANTICOAGULANTS;    ANTICARDIOLIPIN ANTIBODIES;    PHOSPHOLIPID-VESICLES;    HAGEMAN-FACTOR;    FACTOR-XII;    BINDING;    GLYCOLIPIDS;    THROMBOSPONDIN;   

DOI  :  10.1161/01.CIR.0000095030.44185.6A

来源: SCIE

【 摘 要 】

Background - Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. beta(2)-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 beta(2)-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies. Methods and Results - beta(2)-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 mug/well, beta(2)-glycoprotein I reaches half-maximal binding at 2.5 mug/mL, and the binding is saturated at 10 mug/mL. The binding of beta(2)-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant beta(2)-glycoprotein I concentration of 5 mug/mL, maximal binding of beta(2)-glycoprotein I is observed at a coating density of 1 mug/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound beta(2)-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-beta(2)-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 beta(2)-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.

【 授权许可】

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