New Tests to Detect Antiphospholipid Antibodies: Anti-Domain I Beta-2-Glycoprotein-I Antibodies

Beta-2 glycoprotein I (beta(2)GPI) is the main antigenic target for antiphospholipid antibodies (aPL), the serological markers of antiphospholipid syndrome (APS). Domain I (DI) of beta(2)GPI has lately been identified as the main epitope targeted by antibodies reacting against beta(2)GPI. DI is a cryptic epitope, becoming available for autoantibody binding when beta(2)GPI opens from a circular to a fish-hook configuration. Antibodies targeting beta(2)GPI-DI are more frequently detected in patients with a full-blown syndrome than in asymptomatic aPL carriers or in patients with infectious diseases that have reactivity toward the whole molecule. Interestingly, anti-DI antibodies are strongly positively correlated with thrombotic and pregnancy manifestations, enabling identification of patients at higher risk of clinical events. However, available tests to detect anti-DI antibodies still lack standardization. Moreover, some APS patients develop antibodies reacting against beta(2)GPI epitopes other than DI, suggesting that other anti-beta(2)GPI antibody subsets may be clinically relevant. Available evidence on anti-DI antibodies in APS is herein critically reviewed.