ps4 70 anti phosphatidylserine prothrombin antibodies and cardiovascular risk in a sle cohort of patients

Introduction Clinical activity of SLE may wax and wane, but persistent, active systemic inflammation leads to organ damage and rises morbidity and mortality. Early damage is mostly related to disease activity, whereas later damage, in particular atherosclerosis, infections and malignancies are usual complications of long-standing disease and treatment with immunosuppressive agents. One of the major late causes of death in SLE is thrombosis, in particular stroke and myocardial infarction due to CAD. In these patients, the increased cardiovascular morbidity is not fully explained by traditional risk factors and this may lead to under-recognition and under-treatment. Petri, et al. proposed an equation for cardiovascular disease risk in SLE, which combines classical parameters and disease activity markers. Other scores such as the GAPSS(Global AntiPhospholipid Syndrome Score) have been recently evaluated. The importance of aPL in thrombosis in general is well defined, as they constitute the culprit of the so-called anti-phospholipid syndrome(APS). Their role in sustaining the high risk of cardiovascular complications of SLE patients is under-debated. Objective To study the role of the anti-phosphatidylserine/prothrombin(aPS/PT) antibodies, included in the GAPSS score, in contributing to the thrombotic risk of SLE patients. Methods We enrolled 172 patients from Ospedale San Raffaele. 132 patients with SLE(111/132, 84% without secondary APS, SAPS, and 21/132, 16% with SAPS), 19 with primary APS(PAPS) and 21 healthy controls. Each recruited patient was tested for aPS/PT IgG and IgM through ELISA by INOVA Diagnostic, Inc. San Diego, CA USA. Results 36/111 (32.4%) SLE without APS, 15/21 (71.4%) SAPS, 13/19 (68.4%) PAPS and 3/21 (14.3%) healthy donors were aPS/PT+. aPS/PT+SLE patients had a higher cardiovascular risk according to the Petri's score, when compared to aPS/PT-patients, irrespectively of a positive or negative history of overt APS(Mean ±SD Petri' score=20.8±18.1, 14.0±12.8 and 23.8±22.5, 11.6±9.3 respectively, p 10 had also higher prevalence of pregnancy complications. Conclusion aPS/PT antibodies are associated with a high risk of thrombosis and CAD in SLE. aPS/PT assays should be routinely introduced in the management of these patients

Effects of anharmonic strain on phase stability of epitaxial films and superlattices: applications to noble metals

Epitaxial strain energies of epitaxial films and bulk superlattices are studied via first-principles total energy calculations using the local-density approximation. Anharmonic effects due to large lattice mismatch, beyond the reach of the harmonic elasticity theory, are found to be very important in Cu/Au (lattice mismatch 12%), Cu/Ag (12%) and Ni/Au (15%). We find that is the elastically soft direction for biaxial expansion of Cu and Ni, but it is for large biaxial compression of Cu, Ag, and Au. The stability of superlattices is discussed in terms of the coherency strain and interfacial energies. We find that in phase-separating systems such as Cu-Ag the superlattice formation energies decrease with superlattice period, and the interfacial energy is positive. Superlattices are formed easiest on (001) and hardest on (111) substrates. For ordering systems, such as Cu-Au and Ag-Au, the formation energy of superlattices increases with period, and interfacial energies are negative. These superlattices are formed easiest on (001) or (110) and hardest on (111) substrates. For Ni-Au we find a hybrid behavior: superlattices along and like in phase-separating systems, while for they behave like in ordering systems. Finally, recent experimental results on epitaxial stabilization of disordered Ni-Au and Cu-Ag alloys, immiscible in the bulk form, are explained in terms of destabilization of the phase separated state due to lattice mismatch between the substrate and constituents.Comment: RevTeX galley format, 16 pages, includes 9 EPS figures, to appear in Physical Review

PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases

Chromogranin-A production and fragmentation in patients with Takayasu arteritis

BACKGROUND: Chromogranin-A (CgA) is a secretory protein processed into peptides that regulate angiogenesis and vascular cells activation, migration and proliferation. These processes may influence arterial inflammation and remodelling in Takayasu arteritis (TA). METHODS: Plasma levels of full-length CgA (CgA439), CgA fragments lacking the C-terminal region (CgA-FRs) and the N-terminal fragment, CgA1-76 (vasostatin-1, VS-1) were analysed in 42 patients with TA and 20 healthy age-matched controls. Vascular remodelling was longitudinally assessed by imaging. CgA peptides were related to markers of systemic and local inflammation, disease activity and vascular remodelling. RESULTS: Levels of CgA-FRs and VS-1 were increased in TA. Treatment with proton-pump inhibitors (PPIs) and arterial hypertension partially accounted for CgA levels and high inter-patient variability. CgA439, CgA-FRs and VS-1 levels did not reflect disease activity or extent. Markers of systemic or local inflammation correlated with higher CgA-FRs and VS-1 in normotensive patients and with higher CgA439 in hypertensive patients. Treatment with non-biologic anti-rheumatic agents was associated with increased CgA-FRs and a distinctive regulation of CgA processing. Reduced blood levels of anti-angiogenic CgA peptides were associated with vascular remodelling in the groups of patients on PPIs and with arterial hypertension. CONCLUSIONS: The plasma levels of CgA fragments are markedly increased in TA as a consequence of disease- and therapy-related variables. Anti-angiogenic forms of CgA may limit vascular remodelling. Given the effect of the various CgA peptides, it is advisable to limit the therapeutic prescriptions that might influence CgA-derived peptide levels to clearly agreed medical indications until further data become available

Early and Late Response and Glucocorticoid-Sparing Effect of Belimumab in Patients with Systemic Lupus Erythematosus with Joint and Skin Manifestations: Results from the Belimumab in Real Life Setting Study—Joint and Skin (BeRLiSS-JS)

Aim. To assess the efficacy of belimumab in joint and skin manifestations in a nationwide cohort of patients with SLE. Methods. All patients with skin and joint involvement enrolled in the BeRLiSS cohort were considered. Belimumab (intravenous, 10 mg/kg) effectiveness in joint and skin manifestations was assessed by DAS28 and CLASI, respectively. Attainment and predictors of DAS28 remission (<2.6) and LDA (≥2.6, ≤3.2), CLASI = 0, 1, and improvement in DAS28 and CLASI indices ≥20%, ≥50%, and ≥70% were evaluated at 6, 12, 24, and 36 months. Results. DAS28 < 2.6 was achieved by 46%, 57%, and 71% of patients at 6, 12, and 24 months, respectively. CLASI = 0 was achieved by 36%, 48%, and 62% of patients at 6, 12, and 24 months, respectively. Belimumab showed a glucocorticoid-sparing effect, being glucocorticoid-free at 8.5%, 15.4%, 25.6%, and 31.6% of patients at 6, 12, 24, and 36 months, respectively. Patients achieving DAS-LDA and CLASI-50 at 6 months had a higher probability of remission at 12 months compared with those who did not (p = 0.034 and p = 0.028, respectively). Conclusions. Belimumab led to clinical improvement in a significant proportion of patients with joint or skin involvement in a real-life setting and was associated with a glucocorticoid-sparing effect. A significant proportion of patients with a partial response at 6 months achieved remission later on during follow-up

Noninvasive imaging of vascular inflammation

In large-vessel vasculitides, inflammatory infiltrates may cause thickening of the involved arterial vessel wall leading to progressive stenosis and occlusion. Dilatation, aneurysm formation, and thrombosis may also ensue. Activated macrophages and T lymphocytes are fundamental elements in vascular inflammation. The amount and density of the inflammatory infiltrate is directly linked to local disease activity. Additionally, patients with autoimmune disorders have an increased cardiovascular risk compared with age-matched healthy individuals as a consequence of accelerated atherosclerosis. Molecular imaging techniques targeting activated macrophages, neovascularization or increased cellular metabolic activity can represent effective means of noninvasive detection of vascular inflammation. In the present review novel noninvasive imaging tools, that have been successfully tested in humans, will be presented. These include contrast enhanced ultrasonography, which allows detection of neovessels within the wall of inflamed arteries; contrast enhanced cardiovascular magnetic resonance that can detect increased thickness of the arterial wall, usually associated with edema, or mural enhancement using T2 and post-contrast T1-weighted sequences respectively; and positron emission tomography associated with radio-tracers such as [18F]-fluorodeoxyglucose and the new [11C]-PK11195 in combination with computed tomography angiography to detect activated macrophages within the vessel wall. Imaging techniques are useful in the diagnostic work-up of large- and medium-vessel vasculitides, to monitor disease activity and the response to treatments. Finally, molecular imaging targets can provide new clues about the pathogenesis and evolution of immune-mediated disorders involving arterial vessels