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(Circulation. 2003;108:2082.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Sulfatides

Targets for Anti-Phospholipid Antibodies

M. Merten, MD^*; S. Motamedy, MD^*; S. Ramamurthy, MD; F.C. Arnett, MD; P. Thiagarajan, MD

From the Departments of Pathology and Medicine, Baylor College of Medicine, Houston, Tex (M.M., S.M., P.T.); the Department of Internal Medicine, University of Texas Health Sciences Center, Houston, Tex (S.R., F.C.A., P.T.); and the Department of Internal Medicine, Division of Cardiology and Angiology, University Hospital Hamburg-Eppendorf, Germany (M.M.).

Correspondence to Perumal Thiagarajan, MD, VA Medical Center, Mail #113, 2002 Holcombe Blvd, Houston, TX 77030. E-mail perumalt{at}bcm.tmc.edu

Received March 3, 2003; de novo received May 16, 2003; revision received July 29, 2003; accepted July 29, 2003.

Background— Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. ß₂-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 ß₂-glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies.

Methods and Results— ß₂-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, ß₂-glycoprotein I reaches half-maximal binding at 2.5 µg/mL, and the binding is saturated at 10 µg/mL. The binding of ß₂-glycoprotein I also depends on the coating density of sulfatides in the well. At a constant ß₂-glycoprotein I concentration of 5 µg/mL, maximal binding of ß₂-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 ß₂-glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-ß₂-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 ß₂-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.

Key Words: glycoproteins • sulfatides • antibodies • coagulation

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