Dual antibody reactivity to β2-glycoprotein I and protein S: increased association with thrombotic events in the antiphospholipid syndrome

Abstract

The antiphospholipid syndrome (APS) is a thrombotic disorder leading to spontaneous abortions, venous thromboses, myocardial infarctions and strokes. Although the syndrome is associated with characteristic autoantibodies, these tests have poor predictive value for thrombosis. The aim of the study was to determine whether the combined presence of two types of antiphospholipidantibodies can be associated with a high-risk subset of thrombosis-prone patients. One hundred and thirty-four sera from a lupus clinic were tested for antibodies to β2-glycoprotein I (β2GPI), protein S and prothrombin. In a group of 29 patients for whom plasma was available, free (functional) protein S levels were also measured. Autoantibodies to β2GPI and protein S are associated with each other. Dual reactivity to β2GPI and protein S correlates with increased history of thrombotic events (69% of doubly reactive patients) when compared to either type of autoantibodyalone (37% of patients with only anti-β2GPI and 38% with only anti-protein S, P=0.04 and P=0.01, respectively) or neither reactivity (37%). Among 29 patients tested for free (functional, anticoagulant)protein S levels, the lowest levels were found in patients with antibodies to β2GPI and/or protein S, and all four patients with a history of thrombosis had below-normal free protein S levels. These associations were not found with antiprothrombin antibodies. In conclusion dual autoantibodiesto β2GPI and protein S are associated with increased history of thrombosis in the antiphospholipid syndrome.