Can we cure antiphospholipid syndrome?

Antiphospholipid antibody syndrome (APS) is a vasculopathy with recurrent thrombosis and/or miscarriages mediated by autoantibodies against PL-binding proteins (aPL), mainly beta2glycoprotein I (β2GPI). While clotting is the key in vascular APS, thrombosis is not critical for placenta pathology. Despite that, anticoagulant/antiplatelet drugs are the leading treatments, but this is not a ‘one-size-fits-all’ therapy, and recurrences are reported. Additional therapies (e.g. antimalarials, statins) and a better characterization of the individual risk profile may improve the outcome. Nevertheless, we are still unable to ‘cure’ APS. The ideal target would be aPL suppression. However, immunosuppression or even B-cell therapies are not effective. Targeting CD38 on antibody-producing cells or anti-CD19 CAR-T cell therapy are promising alternatives, as well as the chimeric autoantigen receptor T cell therapy, due to the identification of β2GPI as an APS autoantigen. Further therapies aimed at improving clot lysis or affecting β2GPI/anti-β2GPI tissue complex formation are appealing preclinical perspectives.