Elisa Marocchi

Switching tumour necrosis factor α 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)α 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 TNFα antagonist to another because of inadequate efficacy or adverse events. Results: In total, 589 anti-TNFα-naive patients were registered, of whom 165 had a diagnosis of SpA; 7 patients with AS and 15 with PsA received >1 TNFα 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 TNFα antagonist does not preclude the response to another one. Further trials are needed to confirm this preliminary observation.

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 Crohns 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 Crohns 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.

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. &bgr;2 glycoprotein I (&bgr;2GPI) represents a link between autoimmunity and endothelial dysfunction. Recently, &bgr;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 &bgr;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 &bgr;2GPI and Tissue Factor (TF) expression and peripheral blood mononuclear cell response to &bgr;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 &bgr;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 &bgr;2GPI and TF with IMT or FMD was detected. &bgr;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 &bgr;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 &bgr;2GPI-specific T cell reactivity, which is associated with subclinical atherosclerosis.

Subclinical Atherosclerosis in Systemic Lupus Erythematosus and Antiphospholipid Syndrome

Objective— Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with a high prevalence of atherosclerosis. &bgr;2 glycoprotein I (&bgr;2GPI) represents a link between autoimmunity and endothelial dysfunction. Recently, &bgr;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 &bgr;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 &bgr;2GPI and Tissue Factor (TF) expression and peripheral blood mononuclear cell response to &bgr;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 &bgr;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 &bgr;2GPI and TF with IMT or FMD was detected. &bgr;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 &bgr;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 &bgr;2GPI-specific T cell reactivity, which is associated with subclinical atherosclerosis.

FRI0373 Characterization of the Microparticles in the Plasma and Urine of Patients Affected by SLE: Clinical and Laboratory Relationships

Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by heterogeneous clinical manifestations and a complex pathogenesis. The combination of defective clearance of apoptotic cells and a sustained proinflammatory environment could contribute to the chronic inflammatory state. Circulating, heterogeneous subcellular microparticles (MPs) are released from cells and platelets constitutively and upon cellular activation or apoptosis. MPs may reflect the state of their parental cells, and could serve as markers of pathology. In SLE MPs may serve as carriers of autoantigens and constituents of immune complexes. Objectives Aim of the study was to characterize the entire population of the MPs in plasma and urine of SLE patients and healthy controls (HC) and to correlate the presence of MPs with clinical and serological parameters. In addition, we evaluated the annexinV (AnxV)-binding capabilities of MPs. Methods Consecutive SLE patients and sex- and age-matched HC were included in the study. MPs were isolated from citrate-treated plasma and urine and characterized by flow cytometry using AnxV (a probe that binds to the exposed phosphatidilserine - PS) and antibodies to platelet (CD31+CD41+), leukocytes (CD45+), endothelial cells (CD31+CD41-) surface markers. MPs ultra-structure in plasma and urine samples was examined by Transmission electron microscopy in 2 HC and 2 SLE patients. Data were expressed as mean ± standard deviation; Chi squared, Mann-Whitney and Spearman correlation tests were used. A p value <0.05 was considered statistically significant. Results Twenty-eight SLE patients (25F:3M, age 41.8±8.9 yrs, disease duration 159.3±121 months) and 10 HC were studied. The concentration of total MPs was significantly lower in the SLE patients compared to HC (p=0.015); in contrast, urinary Endothelial-MPs (EMPs) were significantly increased in SLE patients (p=0.013). Fig. 1 shows plasma and urinary concentrations of AnxV+ MPs. AnxV- MPs correlated with low C3 and C4 (p=0.039 and p=0.029, respectively) and with the use of immunosoppressants; urinary AnxV+ MPs correlated with hypertension. Total MPs positively correlated with SLEDAI (p=0.011). The concentration of both plasmatic and urinary Leucocytes-MPs correlated with skin involvement (discoid lupus p=0.029, photosensivity p=0.039, alopecia p=0.030); urinary EMPs correlate with the presence of antiphospholipid antibodies (p=0.002); Platelets-MPs, both plasmatic and urinary, correlate with serositis (p=0.009, p=0.005 respectively). Conclusions In conclusion, this study showed altered concentrations and distributions of MP subpopulations in SLE patients as compared with HC. In addition, the results of the study characterized for the first time the population of MPs in urine of SLE patients. AnxV- MPs correlated with low complement, and Leucocytes-MPs with cutaneous manifestations. In aPL positive patients an increased concentration of urinary EMPs was demonstrated suggesting a role of aPL in endothelial damage. Finally, as PS recognition is a fundamental step in phagocytosis of apoptotic bodies and particles, and a defective clearance of apoptosis has been linked to SLE pathogenesis, a lack of PS exposure on MPs could result in impaired MPs turnover and autoimmunity. Disclosure of Interest None declared

AB0555 Systemic Lupus Erythematosus with or Without Anti-Dsdna Antibodies: not so Different

Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease, characterized by the production of a wide range of autoantibodies, resulting from polyclonal B cells activation, impaired apoptotic pathways, or idiotypic network dysregulation. The anti-double stranded DNA antibodies (anti-dsDNA) are considered a specific marker for SLE, due to their high frequency, sensitivity and specificity (57.3% and 97.4%, respectively). Moreover, their identification in other pathological conditions and in healthy subjects is very rare (less than 0.5%). These antibodies have been associated with kidney involvement and disease activity, however, a comparison between large cohorts of SLE patients with or without anti-dsDNA is lacking. Objectives We aimed at evaluating the demographic, clinical, and laboratory features of SLE patients according with the anti-dsDNA status. Methods According with the anti-dsDNA status, we identified three groups of patients: Group 1 (persistently positive); Group 2 (positive at diagnosis who became negative); Group 3 (persistently negative). Disease activity was assessed using the European Consensus Lupus Activity Measurement (ECLAM). Results We evaluated 393 SLE patients (Group 1: 62.3%; Group 2: 13.3%; Group 3: 24.4%). The renal involvement was significantly more frequent in those patients who were persistently positive for anti-dsDNA (P=0.001). Conversely, serositis resulted significant more frequent in those persistently negative (P<0.0001). The anti-RNP and the reduction of C4 serum levels were found significantly more frequently in Group 1 and 2 (P=0.04, P=0.005). The anti-dsDNA status did not influence disease activity (ECLAM group 1 vs group 2 vs group 3 =NS). Finally, the therapeutic approach was not different between the groups except for the use of cyclosporine A which was more frequently prescribed in the persistently positive patients (60 patients, 24.5%) compared to Group 2 and 3 [9 (17.3%) and 12 (12.5%) patients, respectively; P=0.01]. Conclusions The main clinical feature associated with anti-dsDNA positivity is the kidney involvement. Nonetheless, disease activity evaluated with ECLAM, thus with an index which does not include anti-dsDNA evaluation, does not seem to be influenced by the presence of anti-dsDNA. Disclosure of Interest None declared

Subclinical Atherosclerosis in Systemic Lupus Erythematosus and Antiphospholipid SyndromeSignificance

Objective— Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with a high prevalence of atherosclerosis. &bgr;2 glycoprotein I (&bgr;2GPI) represents a link between autoimmunity and endothelial dysfunction. Recently, &bgr;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 &bgr;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 &bgr;2GPI and Tissue Factor (TF) expression and peripheral blood mononuclear cell response to &bgr;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 &bgr;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 &bgr;2GPI and TF with IMT or FMD was detected. &bgr;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 &bgr;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 &bgr;2GPI-specific T cell reactivity, which is associated with subclinical atherosclerosis.

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

Objective— Systemic Lupus Erythematosus (SLE) and antiphospholipid syndrome (APS) are associated with a high prevalence of atherosclerosis. &bgr;2 glycoprotein I (&bgr;2GPI) represents a link between autoimmunity and endothelial dysfunction. Recently, &bgr;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 &bgr;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 &bgr;2GPI and Tissue Factor (TF) expression and peripheral blood mononuclear cell response to &bgr;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 &bgr;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 &bgr;2GPI and TF with IMT or FMD was detected. &bgr;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 &bgr;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 &bgr;2GPI-specific T cell reactivity, which is associated with subclinical atherosclerosis.

THU0175 T cell reactivity to β2 glycoprotein I in systemic lupus erythematosus and anti-phospholipid syndrome: Correlation with subclinical atherosclerosis

Background Systemic lupus erythematosus (SLE) and anti-phospholipid syndrome (APS) patients present a high prevalence of atherosclerosis associated with both traditional and disease-related risk factors. β2 glycoprotein I (β2GPI), the main antigen in APS, seems to represent a link between autoimmunity and endothelial dysfunction which is the earliest atherosclerotic lesion. Recently, β2GPI reactive T cells have been identified; however, their role in the atherosclerosis is still unknown. Objectives Aim of this study was to evaluate early atherosclerosis in SLE and APS patients, correlate subclinical atherosclerosis with traditional and disease-related risk factors and investigate T cell reactivity to β2GPI and its relationship with the atherosclerotic process. Methods We enrolled 50 SLE and 18 primary APS patients and 25 controls. Demographic and clinical data, including traditional cardiovascular risk factors, were recorded. Blood samples were collected to investigate autoantibodies and lipid profile. Monocyte β2GPI and Tissue Factor (TF) expression and peripheral blood mononuclear cells (PBMCs) proliferation after β2GPI stimulation were evaluated. Brachial artery Doppler ultrasound for flow-mediated dilation (FMD) and carotid arteries ultrasound for intima-media thickness (IMT) were performed. Results We detected an increase in mean IMT (mIMT) (0.69 mm ± 0.12) and a decrease in FMD% (6.5±6.6) in SLE patients versus controls (p<0.05 and p=0.0001, respectively) and a decrease in FMD% in APS patients (13.4±12.3) versus controls (p<0.05). Univariate analysis demonstrated a correlation between atherosclerotic lesions and traditional and disease related risk factors; multivariate analysis confirmed as independent risk factors only total cholesterol levels, SLICC and steroid dose for SLE, anti-β2GPI and age for APS. Monocyte β2GPI and TF expression was higher in SLE (34.2±18.9 and 69.5±20.6) and APS (36.3±22.7 and 66.9±26.9) than in controls (18.6±13.7 and 18.6±13.7) (p=0.006 and p=0.001, respectively); no correlation between monocyte β2GPI and TF and IMT or FMD% was detected. β2GPI induced PBMC proliferation in 32% of SLE patients, 25% of APS patients and none in the controls. Proliferative response to β2GPI correlated with history of arterial thrombosis, thrombocytopenia and IMT >0.9 mm. Conclusions β2GPI T cell reactivity and its correlation with IMT and arterial thrombosis suggest a role for β2GPI response in the pathogenesis of accelerated atherosclerosis described in SLE and APS patients. Our study shows a subclinical atherosclerosis in SLE and APS patients associated with traditional and disease-related risk factors. Disclosure of Interest None Declared