Antibodies to Phosphatidylserine/Prothrombin Complex in Antiphospholipid Syndrome: Analytical and Clinical Perspectives.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis and/or pregnancy-related morbidity accompanied by persistently positive antiphospholipid antibodies (aPL). Current laboratory criteria for APS classification recommend testing for lupus anticoagulant as well as IgG and IgM anticardiolipin, and beta-2 glycoprotein I (anti-ß2GPI) antibodies. However, there appears to be a subset of patients with classical APS manifestations who test negative for the recommended criteria aPL tests. While acknowledging that such patients may have clinical features that are not of an autoimmune etiology, experts also speculate that these "seronegative" patients may test negative for relevant autoantibodies as a result of a lack of harmonization and/or standardization. Alternatively, they may have aPL that target other antigens involved in the pathogenesis of APS. In the latter, autoantibodies that recognize a phosphatidylserine/prothrombin (PS/PT) complex have been reported to be associated with APS and may have diagnostic relevance. This review highlights analytical and clinical attributes associated with PS/PT antibodies, taking into consideration the performance characteristics of criteria aPL tests in APS with specific recommendations for harmonization and standardization efforts.

Autoantibodies against phosphatidylserine, prothrombin and phosphatidylserine-prothrombin complex: identical or distinct diagnostic tools for antiphospholipid syndrome?

BACKGROUND: To clarify the association and diagnostic utility of measuring antiphosphatidyl serine (aPS), antiprothrombin (aPT) and the antiphosphatidyl serine/prothrombin complex (aPS/PT) antibodies in patients with antiphospholipid syndrome (APS) and recurrent pregnancy loss (RPL). METHOD: We measured IgG and IgM anti-aPS/PT (2 different kits) as well as the aPS and aPT autoantibodies by ELISA. All subjects were also tested for the presence of Lupus anticoagulant (LA), IgG and IgM anti-cardiolipin (aCL) and anti-beta-2 glycoprotein I (ass(2)GPI), and these served as the gold standard unless otherwise indicated. Two groups of patients were studied: (i) APS with RPL and/or thrombosis (n=62); (ii) RPL only (n=66) and a group of healthy women with successful pregnancies (WSP; n=30). RESULTS: The area under curve (AUC) analyses demonstrated significant differences between the aPS/PT (0.980) and aPT (0.850) assays (p=0.002) with no significant differences between the 2 aPS/PT kits or the aPS/PT and aPS assays. The overall agreement between the tested aPL antibodies and lupus anticoagulant (LA) for the APS cohort was very poor but associations between aPL assays were substantial (kappa>0.5) as determined by Cohen kappa analysis. CONCLUSIONS: Our data show a lack of association between aPS/PT antibodies and LA in APS patients with recurrent pregnancy loss. In the evaluation of these patients, there may be redundancy in testing all three markers as the aPT and aPS assays formed part of the aPS/PT antibody repertoire.