The presence of lupus anticoagulant, moderate-to-high levels of IgG and/or IgM antibodies to beta-2 glycoprotein I or cardiolipin in association with at least one of the two major clinical manifestations (thrombosis and/or pregnancy-related morbidity) are required for a diagnosis of definite antiphospholipid syndrome (APS). The realization that certain negatively charged phospholipid (PL) autoantibodies broadly react with antibodies directed against cardiolipin and may be more reliable and specific markers for APS has led to the search for diagnostic assays with greater predictability for disease evaluation and management. This review focuses on the state-of-the-art analytical and clinical performance of IgG and IgM antibodies directed against negatively charged PLs, specifically phosphatidic acid (aPA), phosphatidylinositol (aPI), and phosphatidylserine (aPS), as well as the APhL assay, which contains a proprietary mixture of phospholipid antigens.
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