Laboratory Testing for Non-criteria Antiphospholipid Antibodies: Anti-phosphatidylserine/Prothrombin Antibodies...

Since the discovery that antiphospholipid antibodies (aPL) bind to a cofactor at the phospholipid membrane, the proteins beta-2-glycoprotein I (β2GPI) and prothrombin seemed to be the antigens of importance in the antiphospholipid syndrome (APS). Anti-β2GPI antibodies (aβ2GPI) were soon included in the classification criteria, while anti-prothrombin antibodies (aPT) are still regarded as "non-criteria" aPL. Evidence is accumulating that antibodies against prothrombin are clinically relevant and closely associated with APS and the presence of lupus anticoagulant (LA). Among the non-criteria aPL, anti-phosphatidylserine/prothrombin antibodies (aPS/PT) are one of the most frequently studied aPL. More and more studies illustrate the evidence of the pathogenic capacity of these antibodies. aPS/PT IgG and IgM are associated with arterial and venous thrombosis, show an overlap with LA presence, and are frequently present in triple-positive patients, regarded as patients at highest risk for APS-related clinical symptoms. Moreover, the association of aPS/PT with thrombosis increases with higher titers, confirming that presence of aPS/PT consolidates the risk. So far, the added value of aPS/PT on top of the criteria aPL to diagnose APS is not clear with opposing findings in literature. Described in this chapter is the procedure for detecting these antibodies with a commercial ELISA, which can be used to determine the presence of IgG and IgM aPS/PT in human samples. Additionally, general guidelines that will facilitate optimal performance of the aPS/PT assay will be provided.