The antiphospholipid antibody syndrome (APS) is characteristically associated with thrombosis. Heparan sulfate (HS) is a physiologic endothelial cell surface modulator of normal anticoagulation, containing a specific oligosaccharide sequence that binds antithrombin III with high affinity and also is present in heparin, a related glycosaminoglycan. We hypothesized that a subset of antiphospholipid antibodies with high affinity for heparan sulfate/heparin epitopes may inhibit the function of HS, promoting a procoagulant state. Purified IgG from all seven patients with APS studied were reactive with heparin by enzyme-linked immunosorbent assay, whereas none of five controls had antiheparin reactivity. IgG antiheparin antibodies were purified from two APS patients by affinity chromatography on heparin-Sepharose. Specificity studies showed that low-affinity electrostatic interactions clearly did not account for the observed reactivity with heparin, and that APS IgG antiheparin antibodies were specifically reactive with a disaccharide present in the heparin pentasaccharide that binds antithrombin III. Furthermore, APS IgG antiheparin antibodies inhibited heparin-accelerated formation of antithrombin III-thrombin complexes. We conclude that antiheparan sulfate/heparin antibodies may be a cause of autoimmune vascular thrombosis in the antiphospholipid antibody syndrome.
Autoantibodies to heparin from patients with antiphospholipid antibody syndrome inhibit formation of antithrombin III-thrombin complexes [see comments]
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S Shibata, PC Harpel, A Gharavi, J Rand, H Fillit; Autoantibodies to heparin from patients with antiphospholipid antibody syndrome inhibit formation of antithrombin III-thrombin complexes [see comments]. Blood 1994; 83 (9): 2532–2540. doi: https://doi.org/10.1182/blood.V83.9.2532.bloodjournal8392532
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