Subclinical atherosclerosis in systemic lupus erythematosus and antiphospholipid syndrome: focus on ß2GPI-specific T cell response.

OBJECTIVE: Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with a high prevalence of atherosclerosis. ß2 glycoprotein I (ß2GPI) represents a link between autoimmunity and endothelial dysfunction. Recently, ß2GPI 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 ß2GPI 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 ß2GPI and Tissue Factor (TF) expression and peripheral blood mononuclear cell response to ß2GPI 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 ß2GPI 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 ß2GPI and TF with IMT or FMD was detected. ß2GPI 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 ß2GPI 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 ß2GPI-specific T cell reactivity, which is associated with subclinical atherosclerosis.

Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort.

OBJECTIVES: The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70-98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status. METHODS: We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA - (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM). RESULTS: We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA -: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA - (21.1% and 18.7%, resp.; P = 0.001). Serositis resulted significantly more frequent in anti-dsDNA - (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.; P < 0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA - (21.8%, P = 0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P = 0.7). CONCLUSION: Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

Premature subclinical atherosclerosis in pediatric inflammatory bowel disease.

OBJECTIVES: To investigate the risk for developing an early endothelial dysfunction based on increased intima media thickness (IMT) and reduced flow-mediated dilation (FMD) in children with inflammatory bowel disease (IBD), and to evaluate the role of traditional and nontraditional risk factors in determining premature atherosclerosis. STUDY DESIGN: We studied 27 patients with Crohn's disease (CD) and 25 patients with ulcerative colitis (UC) (mean age, 15.2 years; mean duration of disease, 48.05 months); 31 subjects served as controls. Demographic data (age, sex, family history of diabetes, cardiovascular disease, hypertension, hypercholesterolemia), traditional risk factors for atherosclerosis (blood pressure, body mass index, active and passive smoking, dyslipidemia), and UC and CD activity indexes (Pediatric Ulcerative Colitis Activity Index and Pediatric Crohn's Disease Activity Index, respectively) were collected. The IMT of the carotid arteries was measured by high-resolution B-mode ultrasound, and endothelial function was evaluated by FMD in the brachial artery in response to reactive hyperemia. RESULTS: Compared with controls, patients with CD had significantly greater exposure to passive smoking and had lower body mass index and high-density lipoprotein cholesterol values. IMT was significantly higher in patients than controls (P < .0001), and the percentage of FMD was significantly lower in both patients with CD (P < .0001) and patients with UC (P < .01) versus controls. In multivariate analysis, diagnosis of IBD was an independent risk factor for atherosclerosis. CONCLUSION: Premature endothelial dysfunction occurs in pediatric IBD. This represents a new challenge in the management of pediatric IBD, leading to prevention strategies of cardiovascular disease.

Switching tumour necrosis factor alpha antagonists in patients with ankylosing spondylitis and psoriatic arthritis: an observational study over a 5-year period.

OBJECTIVE: To evaluate the clinical response after switching from one tumour necrosis factor (TNF)alpha antagonist to another in patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: In this ongoing, longitudinal, observational study, data were prospectively collected on efficacy and safety since 2000 for patients starting biological treatments. The present analysis was restricted to patients with a diagnosis of spondyloarthropathy (SpA) who switched from one TNFalpha antagonist to another because of inadequate efficacy or adverse events. RESULTS: In total, 589 anti-TNFalpha-naive patients were registered, of whom 165 had a diagnosis of SpA; 7 patients with AS and 15 with PsA received >1 TNFalpha antagonist. Two patients with PsA were treated with all the drugs. In all, 16 subjects switched from infliximab to etanercept, 7 from etanercept to adalimumab and 1 from etanercept to infliximab. Overall, a clinical response was seen in 75% of patients who changed from infliximab to etanercept, and in 57.1% who switched from etanercept to adalimumab. CONCLUSIONS: The findings of this study on a selected population of patients with SpA indicate that the failure of an initial TNFalpha antagonist does not preclude the response to another one. Further trials are needed to confirm this preliminary observation.