Monocyte tissue factor induction by activation of beta 2-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 beta2-glycoprotein-I (beta2GPI). 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-gamma when stimulated with beta2GPI in vitro. In this study, we show that stimulation of PBMCs from 20 APS patients with beta2GPI 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 beta2GPI was dose dependent and required CD4+ T lymphocytes and class II MHC molecules. Because monocyte TF induction by beta2GPI 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.
Inflammation and Cytokine Research Units, School of Pathology, University of New South Wales, Sydney, Australia.
S
S
Visvanathan
C L
CL
Geczy
J A
JA
Harmer
H P
HP
McNeil
D017152:Antibodies, Antiphospholipid / Q000097:blood*; D000925:Anticoagulants / Q000276:immunology; D001780:Blood Coagulation Tests; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000097:blood / Q000276:immunology; D005260:Female; D005313:Fetal Death / Q000097:blood / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013925:Thromboplastin / Q000096:biosynthesis* / Q000502:physiology; D013927:Thrombosis / Q000097:blood / Q000276:immunology*; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I; D013925:Thromboplastin