scholarly journals Effects of Atorvastatin on Atherosclerosis and Atherogenesis in Systemic Lupus Erythematosus: A Pilot Study

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Katharina Benita Sokoll ◽  
Joana Batuca ◽  
Luis Romulo Lopez ◽  
Elizabeth Hensor ◽  
Paul Emery ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Pilot Study ◽  
Lupus Erythematosus ◽  
Colorimetric Assay ◽  
Density Lipoprotein ◽  
Intima Media Thickness ◽  
Favourable Effect ◽  
Systemic Lupus ◽  
Double Blind ◽  
Amyloid A

Objective. The effect of statins on atherogenesis in systemic lupus erythematosus (SLE) is poorly known. To inform a wider trial we performed a pilot study evaluating the intima-media thickness of the common carotid artery (CIMT) and some oxidative [beta-2-glycoprotein-1 complexed with oxidised low density lipoprotein (β2GPIoxLDL)], metabolic [paraoxonase (PON), nitrate (NO3 −), nitrite (NO2 −) and nitrotyrosine (NT)], inflammatory [C-reactive protein (CRP) and serum amyloid A (SAA)], and lipid markers before and after 1 year of treatment with 40 mg of oral atorvastatin (AT). Methods. Randomised, double blind, placebo controlled pilot study on consecutive SLE patients: 17 SLE patients were randomised into the AT arm and 20 into the placebo arm. CIMT was measured by high-resolution sonography, PONa by a spectrophotometric method, NO3 − and NO2 − by a colorimetric assay and oxLDL-β2GPI, NT, CRP, and SAA by Elisa. Results. After correction for age and disease duration oxLDL-β2GPI decreased by 27% (P=0.002) and PON/HDL ratio increased by 12% (P=0.01) but CIMT did not change. Conclusion. This pilot study revealed a decrease of oxLDL-β2GPI (oxidant marker) and an increase of PON/HDL ratio (antioxidant activity) after AT indicating a favourable effect of the drug on atherogenic pathways that should be explored on larger trials.

Double-blind, randomized, placebo-controlled pilot study of leflunomide in systemic lupus erythematosus

Lupus ◽  
2004 ◽  
Vol 13 (8) ◽  
pp. 601-604 ◽  
Author(s):  
L-S Tam ◽  
E K Li ◽  
C-K Wong ◽  
C WK Lam ◽  
C-C Szeto
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Pilot Study ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Double Blind

scholarly journals AB0007 STAT4 RS7574865 G/T POLYMORPHISM AS MARKER OF PREDISPOSITION TO SYSTEMIC LUPUS ERYTHEMATOSUS WITH JUVENILE ONSET

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1038.2-1039
Author(s):  
M. Kaleda ◽  
M. Krylov ◽  
I. Nikishina
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Pilot Study ◽  
Lupus Erythematosus ◽  
Renal Involvement ◽  
Control Group ◽  
Coombs Test ◽  
Systemic Lupus ◽  
Direct Coombs Test ◽  
Positive Direct ◽  
Cutaneous Lupus

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a significant genetic predisposition. Recent studies have identified STAT4 (signal transducers and transcription activators 4) as a susceptibility gene for SLE.Objectives:To investigate the hypothesis of the association of STAT4 rs7574865 G/T polymorphism with the predisposition to SLE in children and its relationship with some of SLE manifestations.Methods:The case-control pilot study included 143 children (39 with SLE and 103 healthy unrelated volunteers as a control group). Diagnosis of SLE was based on 2012 SLICC criteria. STAT4 rs7574865 G/T polymorphism was investigated using allele-specific real-time polymerase chain reaction (RT-PCR).Results:The group of pts with SLE consisted of 29 girls and 10 boys, with an average age of 11.8±3.7 years (from 3 to 17 years) and an average disease duration of 4.1±2.4 years. 79.5% pts had acute cutaneous lupus at the onset, 46.1% - nonscarring alopecia, 71.8% - arthritis, 23.1% - oral and nasal ulcers, 23.1% - serositis, 43.6% - renal involvement, 35.9% –neuropsychiatric disorders. Leucopenia/lymphopenia was found in 71.8% of pts, thrombocytopenia – in 23,1%. ANA were detected in 100% pts, anti-dsDNA – in 79.5%, anti-Sm – in 31.6%, antiphospholipid antibodies - in 7,3%, hypocomplementemia – in 61.5%, positive direct Coombs test – in 35.9 %. Macrophage activation syndrome at the onset was documented in 15.4 % of pts. The distribution of rs7574865 genotypes in the control group showed no significant deviations from the Hardy-Weinberg equilibrium. The distribution of genotype frequencies among pts had statistically significant differences compared to the control (χ2=12.95, p=0.0015): GG-30.8% and 63.1% (p=0.001), GT-56.4% and 33.0% (p=0.018), TT-12.8% and 3.9% (p=0.114), GT+TT - 69.2% and 36.9% (p=0.0005). The frequency of the mutant STAT 4 allele T (polymorphism), was significantly higher in the SLE group than in the control group (41% and 20.4%, respectively; p=0.0007). We identified an association of the T allele with some clinical, laboratory, and immunological disorders in SLE: arthritis (OR 3.9, p=0.0002), acute cutaneous lupus (OR 2.47, p=0.003), nonscarring alopecia (OR 3.12, p=0.002), renal involvement (OR 2.42, p=0.022), leucopenia (OR 2.72, p=0.003), thrombocytopenia (OR 4.88, p=0.002), anti-dsDNA (OR 2.82, p=0.0006), hypocomplementemia (OR 2.34, p=0.012), positive direct Coombs test (OR 3.38, p=0.002).Conclusion:Our pilot study confirmed that the STAT4 rs7574865 G/T polymorphism was associated with the risk of SLE in children and some of SLE manifestations.Disclosure of Interests:None declared

scholarly journals AB0983 LIPID METABOLISM AND DISEASE ACTIVITY IN JSLE PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1785.1-1785
Author(s):  
S. Ganhão ◽  
A. Mendes ◽  
F. Aguiar ◽  
M. Rodrigues ◽  
I. Brito
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lipid Metabolism ◽  
Disease Activity ◽  
Lipid Profile ◽  
Lupus Erythematosus ◽  
Systemic Disease ◽  
Density Lipoprotein ◽  
Systemic Lupus ◽  
Parametric Test ◽  
Bivariate Correlation

Background:Systemic lupus erythematosus (SLE) is an autoimmune systemic disease associated with premature atherosclerosis. Risk factors include dyslipoproteinemia, inflammation, oxidized low-density lipoprotein (LDL), hyperhomocysteinemia and antiphospholipid antibodies. Hyperlipidemic condition is being reported to promote the production of proinflammatory cytokines such as IL-1β, IL-6, and IL-27 and lowering blood lipid levels improves the disease. Oxidative stress is elevated, mainly due to mitochondrial dysfunction, further disrupting lipid metabolism. Some drugs also have an impact on lipid profile, such as chronic steroid use, which worsens LDL, HDL, and TG levels.Objectives:To assess the relationship between lipid profile and disease activity in juvenile SLE (jSLE) patients.Methods:Retrospective study of jSLE patients, fulfilling both 2012 and 2019 EULAR/ACR classification criteria for SLE. Juvenile-onset was defined as age at diagnosis <18 years. Demographics and clinical characteristics were collected. To evaluate the activity of jSLE, the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was used. Statistical analysis was performed with SPSS®. Spearman’s rank non-parametric test or Pearson’s parametric test were used to assess the bivariate correlation for inflammatory and metabolic variables. P value <0.05 was considered significant for all the statistical tests.Results:35 patients were included, with current median (min-max) age of 22 (16-35) years, mean (SD) age of diagnosis of 15.8 (2.4) years; 91.4%female. Median ESR was 19 (2-75) mm/h, CRP 1.65 (0.1-9.6) mg/L, albumin 41.6 (16.7-46.3) g/L, proteinuria 0.2 (0-3) g/dL, leukocyturia 0 (0-1362.7)/uL, erythrocyturia 0 (0-501.9)/uL and anti-double stranded DNA 89.3 (10-800) U/mL. Mean C3 was 102.1 (21.6), C4 17.1 (7.4) mg/dL and creatinine 0.63 (0.1) mg/dL. Median SLEDAI was 2 (0-12). All were ANA positive, 40 % positive for antinucleossome antibodies, 25.7% anti-ribossomal P protein antibody, 11.4% anti-Sm, 8.6% autoantibodies againstβ2-glycoproteinI, 8.6% anti-cardiolipin, 14.3% lupus anticoagulant, 37.1% anti-SSA and 8.6% anti-SSB. Articular manifestations were present in 48.6%, mucocutaneous in 77.1%, haematological in 45.7%, lupus nephritis in 42.9%, serositis in 8.6% and pulmonary interstitial disease in 2.9%. Mean (SD) total cholesterol values (TC) was 165.5 (44.7) mg/dL and LDL 94.5 (29.9) mg/dL. Median high-density lipoprotein was 52 (28-92) and triglycerides (TG) 81.5 (41-253) mg/dL. Median daily prednisolone dose was 5 (0-40) mg. 88.6% were treated with hydroxychloroquine, 31.4% with mychophenolate mophetil and 14.3% with azathioprine. TC was negatively correlated with serum albumin (p=0.043, rho=-378) and positively with SLEDAI (p=0.032; rho= 0.392), proteinuria (p=0.009; rho= 0.469) and leukocyturia (p=0.031; rho= 0.394). A positive correlation was found between LDL and proteinuria (p=0.043; rho= 0.385) and between TG and CRP (p=0.001; rho= 0.575). TG were also positively correlated with prednisolone daily dose (p=0.035; rho= 0.394). Mean LDL was higher in anti-Sm positive patients (p=0.022). No differences were found regarding anti-phospholipids antibodies. Nephritic lupus patients had worse lipid metabolism, but this did not reach statistical significance.Conclusion:In out cohort, increased expression of TC, LDL and TGs is associated with disease activity in SLE. As expected, higher doses of prednisolone also correlated with lipid metabolism.References:[1]Machado D et al. Lipid profile among girls with systemic lupus erythematosus. Rheumatol Int. 2017 Jan;37(1):43-48Disclosure of Interests:None declared

scholarly journals Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarfaraz A. Hasni ◽  
Sarthak Gupta ◽  
Michael Davis ◽  
Elaine Poncio ◽  
Yenealem Temesgen-Oyelakin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Systemic Lupus ◽  
Double Blind ◽  
Premature Cardiovascular Disease ◽  
Increased Risk

AbstractIncreased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study’s primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, −26.5), cholesterol efflux capacity (p = 0.08, CI 95%: −0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.

Stiffness parameters, intima-media thickness and early atherosclerosis in systemic lupus erythematosus patients

Lupus ◽  
2009 ◽  
Vol 18 (3) ◽  
pp. 249-256 ◽  
Author(s):  
F Cacciapaglia ◽  
EM Zardi ◽  
G Coppolino ◽  
F Buzzulini ◽  
D Margiotta ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Intima Media Thickness ◽  
Systemic Lupus ◽  
Media Thickness ◽  
Early Atherosclerosis
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