Background--Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. 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 ₂-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies.

Methods and Results--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 µg/well, ₂-glycoprotein I reaches half-maximal binding at 2.5 µg/mL, and the binding is saturated at 10 µg/mL. The binding of ₂-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant ₂-glycoprotein I concentration of 5 µg/mL, maximal binding of ₂-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 ₂-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-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 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.