IgG and IgM Anti‐Phosphatidylserine/Prothrombin Complex Antibody Detection May Improve Classification Accuracy of Systemic Lupus Erythematosus and Antiphospholipid Antibody Syndrome

Objective Antiphospholipid antibody (aPL) syndrome (APS) classification requires a thrombotic event and detection of lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), or anti–β 2 ‐glycoprotein I (anti‐β 2 GPI) antibodies on two occasions ≥12 weeks apart. Here, we investigated the utility of anti–phosphatidylserine/prothrombin complex (anti‐PS/PT) aPL in patients with APS with and without concurrent systemic lupus erythematosus (SLE) with the aim to improve disease disease classification and clinical care. Methods A total of 1,286 patients were tested for presence of IgA, IgG, and IgM anti‐phosphatidylserine/prothrombin complex (anti‐PS/PT) antibodies along with IgA, IgM, and IgG anti‐β 2 GPI and aCL and LAC assays, including hexagonal phase phospholipid neutralization assay (HPPNA), dilute Russell's viper venom time (dRVVT), and platelet neutralization procedures (PNP). Statistical analyses were performed with the chi‐square test using Bonferroni correction for multiple comparisons. Results A total of 324 patients with SLE, 88 patients with APS, and 54 patients with concurrent SLE and APS had simultaneous testing for IgA, IgG, and IgM anti‐PS/PT, aCL, and anti‐β 2 GPI antibodies and HPPNA, dRVVT, and PNP LAC assays. IgM anti‐PS/PT antibody was sensitive for discriminating patients with SLE ( P = 0.0024), APS ( P < 0.0001), and SLE and APS from those without either diagnosis ( P < 0.0001). IgG anti‐PS/PT antibody discriminated patients with APS ( P < 0.0001) and SLE and APS from those without either diagnosis ( P < 0.0001). Among 46 patients with SLE lacking aCL, anti‐β 2 GPI aPL, LAC, or any clinical manifestation of APS, 35 patients only had IgM anti‐PS/PT antibodies, whereas 11 different patients only had IgG anti‐PS/PT antibodies. Conclusion These results demonstrate a significant utility of IgM and IgG anti‐PS/PT antibody testing for more precise classification of SLE and more sensitive diagnosis and timely treatment of patients with relevant thrombotic clinical manifestations.