[Autoantibodies to heparin polysaccharides bind to vascular endothelial cells]

Heparan sulfate, a glycosaminoglycan component of vascular endothelial proteoglycans, provides the anticoagulant functions associated with heparin on the endothelial cell surface. We have demonstrated the presence of spontaneous occurring antibodies to heparin polysaccharides (HPS) in humans. Elevation of serum anti-HPS antibodies were closely associated with the prevalence of thrombosis or fetal loss in patients with autoimmune disease. Affinity purified anti-HPS antibodies inhibited heparin dependent formation of thrombin-antithrombin III complexes. In order to further analyze these autoantibodies, a murine IgG monoclonal anti-HPS antibody, designated H16, was generated. H16 mAb specifically bound to heparin, heparan sulfate and human umbilical vascular endothelial cells (HUVEC). The binding of H16 mAb to HUVEC was specifically inhibited by heparin. Further, H16 mAb inhibited the binding of antithrombin III to heparin in a dose dependent manner. These results indicate that this mAb could recognize antithrombin III-binding sites on vascular endothelial heparan sulfate, leading to procoagulant states through the inhibition of heparin/heparan sulfate dependent anticoagulant process.