Anti-prothrombin antibodies predict thrombosis in patients with systemic lupus erythematosus: a 15-year longitudinal study

Summary. Objective: To evaluate the role of anti‐prothrombin (anti‐PT) antibodies in predicting thrombosis in patients with systemic lupus erythematosus (SLE). Methods: An inception cohort of 101 SLE patients (12 males, 89 females; mean age 30 ± 8 years), was considered. Clinical and laboratory evaluations were regularly performed during a 15‐year follow‐up (median 108 months) with a special focus on thromboembolic events. Serum samples were collected at time of diagnosis and at least once a year thereafter. IgG and IgM anti‐PT, anti‐cardiolipin (aCL) and anti‐β₂glycoprotein I (β₂GPI) antibodies were measured by enzyme‐linked immunosorbent assay (ELISA); lupus anticoagulant (LAC) was assayed by the dilute Russell’s viper venom time and activated partial thromboplastin time tests. The analytical specificity of anti‐PT ELISA was investigated. The timing of thrombosis occurrence was calculated using the Kaplan–Meier method. Results: In the 15‐year follow‐up, thrombosis occurred in 14 out of the 101 patients: venous thrombosis in nine cases and arterial thrombosis in five. IgG and/or IgM anti‐PT, anti‐β₂GPI and aCL antibodies, and LAC activity were detected in ten, nine, seven, and nine cases, with sensitivity for thrombosis of 71.4%, 64.3%, 50% and 64.3%, respectively. Thrombosis‐free survival was 90% at 5 years and 85.8% at 10 and 15 years, respectively. Thrombosis was predicted by anti‐PT (P = 0.001), anti‐β₂GPI antibodies (P = 0.002) and LAC activity (P = 0.001). Moreover, the risk of thrombosis progressively increased with the number of positive antiphospholipid antibody tests. The presence of four positive antibody tests was associated with a risk of thrombosis thirtyfold higher than in their absence. Conclusions: This longitudinal study shows that IgG anti‐PT antibodies are predictors of thrombosis in SLE patients.