Revisiting antiphospholipid antibodies: from targeting phospholipids to phospholipid binding proteins.

The antiphospholipid syndrome (APS) is a multi-system prothrombotic disorder associated with circulating auto-antibodies directed against various phospholipid-binding proteins. The major clinical manifestations are recurrent arterial or venous thrombosis, but due to its heterogeneity, atypical presentations can obscure the diagnosis. Decisions regarding when to attribute complications to aPL are difficult. The most established tests are lupus anticoagulant (LA) detected by clotting assays and anticardiolipin (aCL) detected by ELISA. Although LA and aCL assays are clinically useful, these tests do not clearly differentiate antibodies with different specificities. Antibodies to beta2GPI are associated with thrombosis in the APS. Although these antibodies are detected by aCL assay (e.g. beta2GPI-dependent aCL), some aCL are not associated with the syndrome (e.g. beta2GPI-independent aCL). Regarding LAs, more studies are needed to determine if it is clinically important to differentiate specificities against beta2GPI or prothrombin. The role of aPLs in the pathogenesis of thrombosis requires further and intensive investigation. If autoantibodies to particular phospholipid binding proteins are shown to be associated with different clinical presentations or to confer different risks, the availability of more accurate diagnostic techniques will be required for the recognition of pathogenic aPLs. By now, clinical judgement, careful exclusion of other etiologies and serial aPL levels are helpful in this regard.