Which are the best biological markers of the antiphospholipid syndrome?

The diagnosis of antiphospholipid syndrome (APS) requires the presence of b oth clinical and biological features. Due to the heterogeneity of antiphosp holipid antibodies (aPL) the laboratory approach for their detection includ es clotting-based tests for lupus anticoagulant (LA) as well as solid-phase assays for anticardiolipin antibodies (aCL). In addition, as it has been s hown that autoimmune aPL recognize epitopes on phospholipid (PL)binding pla sma proteins, assays detecting antibodies to beta 2-glycoprotein I (beta 2- GPI) or prothrombin have been developed. The association between venous or arterial thrombosis and recurrent fetal loss with the presence of conventio nal aPL (LA and/or aCL) has been confirmed by many studies. The LA and IgG aCL at moderate/high titre seem to exhibit the strongest association with c linical manifestations of the APS. Several reports indicate that LA is less sensitive but more specific than aCL for the APS. Assays against PLs other than CL as well as the use of mixtures of PLs have been proposed to improv e the detection of APS-related aPL. Concerning antibodies to PL-binding pro teins (detected in the absence of PLs), there is evidence that anti-beta 2- GPI are closely associated with thrombosis and other clinical features of t he APS. Moreover, these antibodies may be more specific in the recognition of the APS and in some cases may be present in the absence of aPL detected by standard tests. Many issues are still under debate and are discussed in this review such as the problems of standardization of anti-beta 2-GPI assa ys, detection of the IE;A isotype of aCL and anti-beta 2-GPI, the coagulati on profiles of LA in the recognition of the thrombotic risk and the associa tion of particular markers with subsets of patients with APS. (C) 2000 Acad emic Press.