Monocyte tissue factor induction by activation of β2-glycoprotein-I- specific T lymphocytes is associated with thrombosis and fetal loss in patients with antiphospholipid antibodies

Antiphospholipid (aPL) syndrome (APS) is characterized by thromboembolic events, thrombocytopenia, or recurrent miscarriage associated with aPL Abs with specificity for β₂-glycoprotein-I (β2GPI). We recently reported that at least 44% of patients with the APS possess circulating type 1 (Th1) CD4⁺ T cells that proliferate and secrete IFN-γ when stimulated with β2GPI in vitro. In this study, we show that stimulation of PBMCs from 20 APS patients with β2GPI induced substantial monocyte tissue factor (TF) (80 ± 11 TF stimulation index (TF-SI)), whereas no induction was observed using PBMCs from 13 patients with aPL Abs without APS (6 ± 1 TF-SI) or 7 normal and 7 autoimmune controls (5 ± 1 and 3 ± 1 TF-SI, respectively) (p < 0.0001). TF induction on monocytes by β2GPI was dose dependent and required CD4⁺ T lymphocytes and class II MHC molecules. Because monocyte TF induction by β2GPI was observed in all patients with APS, but not in any patient with aPL Abs without APS, this response is a potentially useful predictor for APS in patients with aPL Abs, as well as providing mechanistic insight into thrombosis and fetal loss in these patients.