Relationship of anti beta2-glycoprotein I and anti prothrombin antibodies to thrombosis and pregnancy loss in patients with antiphospholipid antibodies

Abstract

The lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) are clinically relevant because of their association with thrombosis and pregnancy loss. The group of antiphospholipid antibodies (aPL) includes antibodies primarily directed against various phospholipid-binding proteins, mainly beta2-glycoprotein I (beta2GPI) and prothrombin. Some studies suggest that there is an association between the presence of anti beta2GPI antibodies (alphabeta2GPI) of IgG isotype and thrombosis. Therefore, aPL defined according to the plasma protein to which they are directed appear to be more appropriate for the evaluation of their clinical importance. Using home-made ELISAs we evaluated the presence of alphabeta2GPI and antiprothrombin antibodies (anti-II) of both isotypes (IgG and IgM) in a group of 233 patients with LA and/or aCL. Forty-four women had a history of pregnancy loss, 45 patients had a history of venous thrombosis (VT) and 32 of arterial thrombosis (AT). Patients from the autoimmune group (systemic lupus erythematosus and antiphospholipid syndrome) had a higher prevalence of alphabeta2GPI and/or anti-II than those from the miscellaneous group. In the univariate analysis, a significant association was shown between the presence of alphabeta2GPI-IgG (OR 3.2; 95% CI 1.5-6.6) and previous VT, but not AT. Anti-II were related to VT but the multivariate analysis showed that alphabeta2GPI-IgG are the only independent risk factor for VT (OR 3.0; 95% CI 1.3-6.2). The presence of alphabeta2GPI-IgM correlates well with a history of pregnancy loss (OR 2.6; 95% CI 1.1-6.1). The coagulation tests profile showed that the clotting assays were more prolonged in patients having aCL, alphabeta2GPI or anti-II. But a higher prevalence of abnormal results was only found for the dilute Russell viper venom time in patients with VT, as compared to those without thrombosis (94.4% vs. 58.7%, p <0.02). The measurement of alphabeta2GPI of both isotypes could help to identify aPL-positive patients with a higher risk for thrombosis and pregnancy loss, although this association should be confirmed by prospective studies.