Sulfatides: targets for anti-phospholipid antibodies.
BACKGROUND
Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. Beta2-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 beta2-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies.


RESULTS
Beta2-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 microg/well, beta2-glycoprotein I reaches half-maximal binding at 2.5 microg/mL, and the binding is saturated at 10 microg/mL. The binding of beta2-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant beta2-glycoprotein I concentration of 5 microg/mL, maximal binding of beta2-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 beta2-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-beta2-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 beta2-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.
Merten
M
M
Departments of Pathology and Medicine, Baylor College of Medicine, Houston, Tex, USA.
Motamedy
S
S
Ramamurthy
S
S
Arnett
F C
FC
Thiagarajan
P
P
D017153:Antibodies, Anticardiolipin / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000378:metabolism*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007163:Immunosorbent Techniques; D008081:Liposomes / Q000737:chemistry; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D046911:Macromolecular Substances; D011485:Protein Binding / Q000502:physiology; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology; D013433:Sulfoglycosphingolipids / Q000737:chemistry / Q000276:immunology*; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D002308:Cardiolipins; D006023:Glycoproteins; D008081:Liposomes; D046911:Macromolecular Substances; D013433:Sulfoglycosphingolipids; D053482:beta 2-Glycoprotein I