Subclinical Atherosclerosis in Systemic Lupus Erythematosus and Antiphospholipid Syndrome Focus on β2GPI-Specific T Cell Response

Objective Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with a high prevalence of atherosclerosis. 2 glycoprotein I (2GPI) represents a link between autoimmunity and endothelial dysfunction. Recently, 2GPI reactive T cells have been identified; however, their role in atherosclerosis is still under investigation. We evaluated early atherosclerosis in patients with SLE and APS and investigated T cell reactivity to 2GPI and its relationship with atherosclerotic process. Approach and Results Fifty SLE, 18 patients with primary APS (PAPS), and 25 healthy controls were enrolled. Demographic and clinical data, including traditional cardiovascular risk factors, were recorded. Monocyte 2GPI and Tissue Factor (TF) expression and peripheral blood mononuclear cell response to 2GPI stimulation were evaluated. Doppler ultrasound was performed to investigate flow-mediated dilatation (FMD) and carotid intima-media thickness (IMT). We detected an increase in mean IMT and a decrease in FMD in patients with SLE versus controls (P<0.05 and P=0.0001, respectively) and a decrease in FMD in patients with PAPS versus controls (P<0.05). Monocyte 2GPI and TF expression was higher in patients with SLE and PAPS than in controls (P=0.006 and P=0.001, respectively); no correlation of monocyte 2GPI and TF with IMT or FMD was detected. 2GPI induced peripheral blood mononuclear cell proliferation in 32% of patients with SLE, 25% of patients with PAPS yet in none of the controls. Proliferative response to 2GPI correlated with a history of arterial thrombosis, thrombocytopenia, and IMT >0.9 mm. Conclusions A significant percentage of patients with SLE and PAPS show a 2GPI-specific T cell reactivity, which is associated with subclinical atherosclerosis.