Background: Systemic lupus erythematosus (SLE) patients have tendencies of accelerated atherosclerosis (AS) which can only partly be explained by traditional cardiovascular disease (CVD) risk factors. Imbalanced inflammation also plays a vital role. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new therapeutic target for AS for its dual mechanisms in lipids and inflammation. We aimed to assess serum PCSK9 concentrations in SLE patients and its possible role in atherogenesis of SLE. Methods: Ninety SLE patients and 50 healthy controls were included. SLE patients were further divided into SLE-AS and SLE-NonAS subgroups, according to the carotid intima-media thickness (cIMT). Traditional CVD risk factors, inflammatory biomarkers and PCSK9 concentrations were compared between: (I) SLE patients and controls; (II) SLE-AS subgroup and SLE-NonAS subgroup; (III) SLE patients with and without lupus nephritis (LN). Correlational analysis, univariate and multivariate linear regression analysis were applied to analyze the association between PCSK9 levels and disease parameter in SLE patients. Effects on PCSK9 concentrations by monotherapy with hydroxychloroquine (HCQ), which is thought having protective effects against AS in SLE, were investigated by follow-up analysis in 15 SLE patients. Results: We found that SLE patients had significantly elevated serum PCSK9 levels than controls, especially in SLE-As subgroup or those with LN, accompanied with higher ratio of cIMT thickening. Correlational analysis showed PCSK9 concentrations correlated with C-reactive protein (CRP) levels, age and erythrocyte sedimentation rate (ESR). Univariate and multivariate linear regression revealed that only CRP, but not age or ESR was positive predictors of PCSK9. Interestingly, monotherapy with HCQ for three months significantly reduced PCSK9 and CRP levels in inactive SLE patients. Conclusions: Our results suggested that elevated PCSK9 levels in SLE are probably associated with atherogenic inflammation in SLE. HCQ, which is thought having protective effects against AS in SLE, can effectively reduce PCSK9 levels in SLE patients.

Background: Layer-specific speckle-tracking echocardiography (STE) is a noninvasive approach that assesses subclinical left ventricular dysfunction. We aimed to investigate the (I) alteration of layer-specific STE parameters and the dyssynchrony index; and (II) the disease parameters associated with layer-specific STE change in drug-naïve patients with new-onset systemic lupus erythematosus (SLE) without cardiac symptoms.Methods: Thirty-five drug-naïve patients with new-onset SLE and twenty-five healthy controls were enrolled. All individuals received both conventional echocardiographic and two-dimensional STE assessment. The data of layer-specific global longitudinal strain (GLS), global circumferential strain (GCS), and peak systolic dispersion (PSD) were acquired in layer-specific STE.Results: All patients had a normal left ventricular ejection fraction (LVEF)(mean LVEF: 58%) and conventional echocardiographic parameters were comparable between patients and controls. Decreased layer-specific GLS and elevated PSD were observed in SLE patients (whole layer GLS:

We investigated whether serum CXC ligand 13 protein (CXCL13) levels correlate with the circulating plasmablasts and memory B-cells alteration in systemic lupus erythematosus (SLE) patients. The diagnostic use of CXCL13 concentrations in active lupus was also analyzed.A total of 36 SLE patients and 18 healthy controls were included. Serum CXCL13 levels were examined by enzyme-linked immunosorbent assay. The frequency and absolute count of circulating plasmablasts and memory B cells were analyzed by flow cytometry. Receiver operating characteristic curves (ROC curves) were generated to analyze the utility of serum CXCL13 level and plasmablasts frequency as tools for the recognition of active SLE.Elevation of serum CXCL13 levels, higher plasmablasts frequency, and reduction of memory B-cells count were observed in SLE patients, compared with healthy controls. Interestingly, correlational analyses showed not only significantly positive association between CXCL13 levels and SLE Disease Activity Index (SLEDAI) or plasmablasts frequency, but an inverse correlation between CXCL13 concentration and memory B-cell count. ROC curves showed that serum CXCL13 level and plasmablasts frequency were practical in identifying active disease from overall SLE patients, with considerable accuracy.Serum CXCL13 levels correlate with the alteration of plasmablasts and memory B cells in SLE. CXCL13 may be used as a practical tool in judgment of active SLE.

BackgroundSystemic lupus erythematosus (SLE) patients have tendencies of accelerated atherosclerosis (AS), which is refractory to statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a new therapeutic target for AS for its dual mechanisms in lipids metabolism and inflammation. PCSK9 inhibitors had proved to be highly promising cardiovascular disease (CVD) drugs [1]. Our previous study suggested that Toll-like recetor 4(TLR4) signal participates in the atherosclerotic inflammation of murine model of lupus with AS [2].ObjectivesTo investigate the role of PCSK9 in atherosclerotic process of lupus and the association between TLR4 and PCSK9 in athergenic inflammation of murine model of lupus with AS.Methods90 SLE patients and 50 healthy controls were included. According to carotid intima-media thickness (cIMT), SLE patients were further divided into SLE-AS and SLE-NonAS subgroups (cut-off point: 1.0mm). Traditional CVD risk factors, inflammatory biomarkers and PCSK9 concentrations were compared between: (I) SLE patients and controls; (II) SLE-AS subgroup and SLE-NonAS subgroup. Correlational analysis and multivariate linear regression analysis were applied to analyze the association between PCSK9 levels and disease parameter, and the predictors of PCSK9 levels in SLE patients. Effects on PCSK9 concentrations by monotherapy with hydroxychloroquine (HCQ), which is thought having protective effects against CVD in SLE, were investigated by follow-up analysis in 15 SLE patients with inactive disease (SLEDAI=2). In animal experiment, murine model of SLE with AS was set up by intraperitoneally injection of lipopolysaccharides (LPS) in ApoE-/- mice. 30 female ApoE-/- mice were respectively administrated with LPS (SLE+AS group, n=10), saline (AS group, n=10) and LPS plus injection of lentiviruse-PCSK9 small hairpin RNA targeting the mouse PCSK9 gene into the tail vein to interfere PCSK9 expression (SLE+AS+PCSK9i group, n=10). 10 female C57BL/6 mice were included as controls. Serum concentrations of PCSK9 and inflammatory biomarkers including TNF-α and IL-1β, atherosclerotic lesion, lipids parameters, expression of PCSK9, TLR4 and NF-κB p65 in atherosclerotic plaque were assessed.ResultsCharacteristics of SLE patients and controls were listed in Table 1. SLE patients had significantly elevated serum PCSK9 levels than controls, especially in SLE-AS subgroup, accompanied with higher ratio of cIMT thickening. Correlational analysis showed PCSK9 concentrations correlated with C-reactive protein (CRP) levels, age and erythrocyte sedimentation rate (ESR), but not lipids parameters. Univariate and multivariate linear regression revealed that only CRP, but not age or ESR was positive predictors of PCSK9. Monotherapy with HCQ for 3 months significantly reduced PCSK9 levels in inactive SLE patients (Table 2, Figure 1). Mice in SLE+AS group had significantly higher serum PCSK9 concentrations than mice in AS group and C57BL/6 mice. Immunohistochemistry showed that PCSK9 overexpression was observed in SLE+AS mice than those in A...

BackgroundSLE patients have a tendency of accelerated atherosclerosis(AS) which can only partly be explained by traditional risk factors for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9), which is a protease associated with cardiovascular risk that regulates both cholesterol metabolism and inflammatory reaction, had been regarded as a highly promising therapeutic target for cardiovascular disease[.1 Recent study had demonstrated that SLE patients with lupus nephritis(LN) had much higher risk of atherosclerosis[.2 ObjectivesTo assess serum PCSK9 concentrations and the possible factors linked with PCSK9 variation in SLE/LN patients.Methods47 SLE patients and 30 healthy controls were included. Traditional cardiovascular risk factors were compared. According to cIMT, SLE patients were divided into two subgroups (SLE-AS subgroup and SLE-NonAS subgroup, cut-off point is 1.0 mm). PCSK9 concentrations were compared between:1SLE patients and controls;2SLE-AS subgroup and SLE-NonAS subgroup;3SLE patients with and without lupus nephritis(LN). The correlational analyses between PCSK9 levels and disease parameters were undergone.ResultsThe differences of lipids parameters, body mass index (BMI), uric acid(UA) between SLE group and controls had no statistical significance. Even so, the ratio of cIMT thickening were higher in SLE patients, when compared with healthy controls (23.40% versus 6.67%, p=0.05). Serum PCSK9 levels were also significantly elevated in SLE patients than controls (median of PCSK9 level: 390.53 ng/ml versus 292.44 ng/ml, p<0.05). Patients in SLE-AS subgroup had even higher PCSK9 and C-reactive protein(CRP) levels than those in SLE-NonAS subgroup (median of PCSK9 level: 516.41 ng/ml versus 364.47 ng/ml, p<0.05; median of CRP level: 4.56 mg/L versus 1.05 mg/L, p<0.01) (figure 1). PCSK9 levels correlated with CRP levels, but not with age, disease activity, lipids characteristics, BMI or UA levels, particularly in female patients (table 1). Despite of no statistical significance, the ratio of lupus nephritis were higher in SLE-AS subgroup than those in SLE-NonAS subgroup (63.64% versus 44.44%, p>0.05). SLE patients with LN had higher PCSK9 concentrations than those without LN evidence(509.53±131.69 ng/ml versus 332.02±92.72 ng/ml, p<0.001).Abstract AB1365 – Table 1Correlational analysis of PCSK9 levels and disease parameters in SLE patients.Variablesrsp-value Age(years)−0.0140.927SLEDAI0.0920.539BMI(kg/m2)−0.1200.420Cholesterol(mmol/l)−0.0120.935LDL cholesterol(mmol/l)0.0020.989ApoA1(g/l)0.0110.943ApoB(g/l)0.1810.223Triglycerides(mmol/l)−0.0200.896HDL cholesterol(mmol/l)−0.1120.453Fasting blood glucose(mmol/l)−0.1930.193Uric acid(μmol/l)−0.0790.599CRP(mg/l)0.3510.016CRP(mg/l) in female patients0.4870.001Abstract AB1365 – Figure 1ConclusionsElevation of PCSK9 concentrations can be observed in SLE patients, especially in those with LN or atherosclerosis. PCSK9. PCSK9 is probably linked with low-grade inflammation participating in the pathogenesis of atherosclerosis in SLE/LN patien...