title: Subclinical atherosclerosis in systemic lupus erythematosus and antiphospholipid syndrome: focus on β2GPI-specific T cell response.
abstract: OBJECTIVE
  Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with a high prevalence of atherosclerosis. β2 glycoprotein I (β2GPI) represents a link between autoimmunity and endothelial dysfunction. Recently, β2GPI 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 β2GPI and its relationship with atherosclerotic process.
  
  
  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 β2GPI and Tissue Factor (TF) expression and peripheral blood mononuclear cell response to β2GPI 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 β2GPI 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 β2GPI and TF with IMT or FMD was detected. β2GPI 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 β2GPI 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 β2GPI-specific T cell reactivity, which is associated with subclinical atherosclerosis.
authors.affiliation: From the Rheumatology Unit (F.C., F.R.S., C.A., F.C., E.M., G.V.), Atherosclerosis Unit (A.M., M.A.), and Internal Medicine D (M.P.), Department of Internal Medicine and Medical Specialties and Department of Experimental Medicine (A.C., M.S.), Sapienza University of Rome, Rome, Italy; and Department of Infectious, Parasitic, and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, Italy (B.B., E.P., R.R.).
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Conti
authors.forename: Francesca Romana
authors.initials: FR
authors.lastname: Spinelli
authors.forename: Cristiano
authors.initials: C
authors.lastname: Alessandri
authors.forename: Massimo
authors.initials: M
authors.lastname: Pacelli
authors.forename: Fulvia
authors.initials: F
authors.lastname: Ceccarelli
authors.forename: Elisa
authors.initials: E
authors.lastname: Marocchi
authors.forename: Anna
authors.initials: A
authors.lastname: Montali
authors.forename: Antonella
authors.initials: A
authors.lastname: Capozzi
authors.forename: Brigitta
authors.initials: B
authors.lastname: Buttari
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Profumo
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sorice
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
authors.forename: Rachele
authors.initials: R
authors.lastname: Riganò
mesh_terms: D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000276:immunology; D050197:Atherosclerosis / Q000209:etiology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000453:epidemiology; D059168:Carotid Intima-Media Thickness; D002455:Cell Division; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D018056:Hemorheology; D006801:Humans; D059425:Interferon-gamma Release Tests; D008075:Lipoproteins, HDL / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D012307:Risk Factors; D037182:T-Cell Antigen Receptor Specificity; D013925:Thromboplastin / Q000096:biosynthesis / Q000235:genetics; D014664:Vasodilation; D055815:Young Adult; D053482:beta 2-Glycoprotein I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D008075:Lipoproteins, HDL; D053482:beta 2-Glycoprotein I; D013925:Thromboplastin
keywords: antiphospholipid syndrome; atherosclerosis; beta 2-glycoprotein I; systemic lupus erythematosus