β₂-Glycoprotein-1 autoantibodies from patients with antiphospholipid syndrome are sufficient to potentiate arterial thrombus formation in a mouse model.

Antiphospholipid syndrome is characterized by thrombosis, recurrent fetal loss, and the presence of the lupus anticoagulant, anticardiolipin antibodies, or anti-β(2)-glycoprotein-1 (anti-β(2)-GP1) antibodies. Although anti-β(2)-GP1 antibodies have been documented as a biomarker for diagnosis of antiphospholipid syndrome, their direct role in the pathogenesis of thrombosis is unknown. We have demonstrated using intravital microscopy that anti-β(2)-GP1 autoantibodies purified from the sera of patients with antiphospholipid syndrome complicated by thrombosis greatly amplify thrombus size after laser-induced vessel wall injury in live mice. Anti-β(2)-GP1 autoantibodies from 3 patients with antiphospholipid syndrome were affinity-purified using human β(2)-GP1 bound to agarose. The effects of purified anti-β(2)-GP1 IgG autoantibodies, of anti-β(2)-GP1-depleted IgG, and of IgG from normal human sera on thrombus formation were measured in mice after arterial injury in the cremaster muscle. Before injury, purified anti-β(2)-GP1 IgG autoantibodies, anti-β(2)-GP1 antibody-depleted IgG, or IgG from normal human sera were infused. Increasing amounts of purified anti-β(2)-GP1 autoantibodies increased thrombus size in a dose-dependent manner, whereas neither anti-β(2)-GP1 antibody-depleted IgG nor IgG from normal serum affected thrombus size. These results indicate that anti-β(2)-GP1 IgG autoantibodies in antiphospholipid syndrome patient sera are not only a marker of antiphospholipid syndrome but are directly involved in the pathogenesis of thrombosis.