scholarly journals Plasma Sphingolipid Profile Associated With Subclinical Atherosclerosis and Clinical Disease Markers of Systemic Lupus Erythematosus: Potential Predictive Value

2021 ◽  
Vol 12 ◽  
Author(s):  
Samar M. Hammad ◽  
Olivia C. Harden ◽  
Dulaney A. Wilson ◽  
Waleed O. Twal ◽  
Paul J. Nietert ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
African American ◽  
Lupus Erythematosus ◽  
Predictive Value ◽  
Subclinical Atherosclerosis ◽  
Plaque Burden ◽  
Systemic Lupus ◽  
Cvd Risk ◽  
Plaque Area ◽  
Increased Risk

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects females more than males, with African Americans developing more severe manifestation of the disease. SLE patients are at increased risk for cardiovascular disease (CVD), and SLE women 35-44 years old have 50 fold the incidence rate of CVD. Because SLE patients do not follow the typical age and gender pattern for CVD, but instead an accelerated disease course, the traditional biomarkers of elevated LDL and total cholesterol levels do not accurately assess their CVD risk. Recently, we have reported that African American SLE patients had higher ceramide, hexosylceramide, sphingosine and dihydrosphingosine 1-phosphate levels compared to their healthy controls, and those with atherosclerosis had higher sphingomyelin and sphingoid bases levels than those without (PLoS One. 2019; e0224496). In the current study, we sought to identify sphingolipid species that correlate with and pose the potential to predict atherosclerosis severity in African American SLE patients. Plasma samples from a group of African American predominantly female SLE patients with well-defined carotid atherosclerotic plaque burden were analyzed for sphingolipidomics using targeted mass spectroscopy. The data demonstrated that at baseline, plaque area and C3 values correlated inversely with most lactoceramide species. After one-year follow-up visit, values of the change of plaque area correlated positively with the lactoceramide species. There was no correlation between LDL-C concentrations and lactoceramide species. Taken together, lactocylcermide levels may have a ‘predictive’ value and sphingolipidomics have an added benefit to currently available tools in early diagnosis and prognosis of African American SLE patients with CVD.

scholarly journals Unique monocyte transcriptomic profiles are associated with preclinical atherosclerosis in women with systemic lupus erythematosus (SLE)

2020 ◽  
Author(s):  
Laurel Woodridge ◽  
Paul Ashford ◽  
Elvira Chocano ◽  
George Robinson ◽  
Kirsty Waddington ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cardiovascular Risk ◽  
Lupus Erythematosus ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Bioinformatic Analysis ◽  
Systemic Lupus ◽  
Cvd Risk ◽  
Increased Risk ◽  
Preclinical Atherosclerosis

Women with Systemic Lupus Erythematosus (SLE) show significantly increased cardiovascular risk compared to the general population. However, despite CVD being a major cause of morbidity and mortality for these women, this increased risk is not managed clinically and tools to dissect and predict their cardiovascular risk are lacking. Notably, this elevated CVD risk is not captured by traditional risk factors. To explore molecular programs underlying asymptomatic atherosclerosis in SLE we used a well-characterised cohort of CVD-free women with SLE, scanned for asymptomatic atherosclerotic plaques using non-invasive ultrasound imaging of the carotid and femoral arteries. We investigated the transcriptomic profiles of CD14+ circulating monocytes in women with SLE with or without preclinical atherosclerosis. We identified unique monocytic gene expression profiles that distinguished the presence of preclinical plaques in women with SLE. In addition, advanced bioinformatic analysis revealed functional pathways and interactions between the genes identified that could explain mechanistic differences in plaque formation. We propose that these molecular signatures could help understand why a subset of women with SLE are predisposed to develop atherosclerosis and at higher risk of developing clinical CVD. Collectively with other efforts, these molecular insights will help to better define atherosclerosis in the context of SLE which will be critical for future patient stratification and identification of anti-atherosclerotic therapies.

Cardiovascular disease in systemic lupus erythematosus

2021 ◽  
Vol 2 (3) ◽  
pp. 157-172
Author(s):  
Maureen McMahon ◽  
Richard Seto ◽  
Brian J. Skaggs
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Cardiovascular Disease ◽  
Lupus Erythematosus ◽  
Cardiovascular Events ◽  
Subclinical Atherosclerosis ◽  
Cardiac Risk ◽  
Systemic Lupus ◽  
Cardiac Risk Factors ◽  
Increased Risk

Abstract There is a well-known increased risk for cardiovascular disease that contributes to morbidity and mortality in systemic lupus erythematosus (SLE). Major adverse cardiovascular events and subclinical atherosclerosis are both increased in this patient population. While traditional cardiac risk factors do contribute to the increased risk that is seen, lupus disease-related factors, medications, and genetic factors also impact the overall risk. SLE-specific inflammation, including oxidized lipids, cytokines, and altered immune cell subtypes all are likely to play a role in the pathogenesis of atherosclerotic plaques. Research is ongoing to identify biomarkers that can help clinicians to predict which SLE patients are at the greatest risk for cardiovascular disease (CVD). While SLE-specific treatment regimens for the prevention of cardiovascular events have not been identified, current strategies include minimization of traditional cardiac risk factors and lowering of overall lupus disease activity.

Incidence and predictors of aorta calcification in patients with systemic lupus erythematosus

Lupus ◽  
2019 ◽  
Vol 28 (3) ◽  
pp. 275-282 ◽  
Author(s):  
L Hu ◽  
Z Chen ◽  
Y Jin ◽  
B Jiang ◽  
X Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Coronary Artery ◽  
Lupus Erythematosus ◽  
Coronary Artery Calcification ◽  
Activity Index ◽  
Subclinical Atherosclerosis ◽  
Agatston Score ◽  
Systemic Lupus ◽  
Sledai Score ◽  
Increased Risk

Objective Artery calcification, as subclinical atherosclerosis, is attracting attention. The aim of this study was to determine the prevalence and risk factors of artery calcification in patients with systemic lupus erythematosus. Methods 641 patients with systemic lupus erythematosus were enrolled in the study. Demographic, clinical, and laboratory characteristics were collected. Calcification score was quantified from the multi-detector computed tomography scan image using the Agatston Score method. Results The total incidence of artery calcification was 25.9% (166/641), of which the percentages of aorta calcium and coronary artery calcification were 23.1% (148/641) and 8.4% (54/641), respectively. In multivariate models, systemic lupus erythematosus patients with artery calcification had longer disease duration than patients without artery calcification ( p < 0.05). Presence of serositis (OR 2.559, 95%CI 1.414–4.632), pneumonia (OR 2.022, 95%CI 1.102–3.711) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (OR 1.049, 95%CI 1.004–1.095) were independently associated with increased risk of aorta calcium, while the duration of corticosteroids use (OR 1.039, 95%CI 1.002–1.078) and cyclophosphamide therapy (OR 8.251, 95%CI 2.496–27.279) were independently associated with increased risk of coronary artery calcification in systemic lupus erythematosus patients. In systemic lupus erythematosus patients, aorta calcium was prone to occur at a younger age compared to coronary artery calcification, and aorta calcium score was positively correlated with age. Conclusions Systemic lupus erythematosus patients had a much earlier onset and higher incidences of aorta calcium than coronary artery calcification. Presence of serositis, pneumonia, and higher SLEDAI score may predict increased risk of aorta calcium.

scholarly journals Subclinical atherosclerosis in young Thai adults with juvenile-onset systemic lupus erythematosus

2016 ◽  
Vol 10 (2) ◽  
Author(s):  
Nalinee Pattrakornkul ◽  
Patamakom Pruangprasert ◽  
Prakul Chanthong ◽  
Ratana Chawanasuntorapoj ◽  
Anirut Pattaragarn
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Subclinical Atherosclerosis ◽  
Disease Stage ◽  
Healthy Population ◽  
Systemic Lupus ◽  
Juvenile Onset ◽  
Persistent Proteinuria ◽  
Increased Risk

AbstractBackgroundCardiovascular disease (CVD) is a leading cause of morbidity and mortality in adult patients with systemic lupus erythematosus (SLE). Increased risk of CVD and atherosclerosis has been demonstrated in children with SLE. However, evidence of atherosclerosis in adults with juvenile-onset SLE is limited and their additional CVD risk factors unclear.ObjectivesTo investigate the presence of subclinical atherosclerosis in young Thai adults with juvenile-onset SLE, and evaluate atherosclerotic risk factors.MethodsWe recruited a cohort of patients aged 18-40 years who had been diagnosed SLE before the age of 18 years for this observational study. Patients with chronic kidney disease stage IV or V, alcoholism, chronic liver disease, or life threatening illness were excluded. Common carotid intima-media thickness (CCIMT) was measured. Clinical and laboratory parameters, treatment, and SLE-related factors, which could be risk factors for atherosclerosis and classic risk factors were obtained.ResultsWe enrolled 29 patients (24 female). Their mean age was 25.1 years and mean disease duration 11.3 years. The age of participants, persistent proteinuria and use of cyclosporin correlated with increased CCIMT by multivariable analysis (P = 0.02, 0.02, and 0.03, respectively). These patients had significantly abnormal CCIMT when compared with a healthy population (mean 690 (SD 150) μm versus mean 447 (SD 76) μm, respectively; P < 0.001).ConclusionsSubclinical atherosclerosis, identified by abnormal CCIMT, appears in young adults with juvenile-onset SLE. The CCIMT abnormality progresses with increasing age, and persistent proteinuria and use of cyclosporin appears to increase the risk for atherosclerosis.

scholarly journals POS0706 PERFORMANCES OF DIFFERENT CLASSIFICATION CRITERIA FOR SYSTEMIC LUPUS ERYTHEMATOSUS IN A SINGLE CENTER COHORT FROM TURKEY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 602.1-603
Author(s):  
E. S. Torun ◽  
E. Bektaş ◽  
F. Kemik ◽  
M. Bektaş ◽  
C. Cetin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Positive Predictive Value ◽  
Negative Predictive Value ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Predictive Value ◽  
Sjogren's Syndrome ◽  
Classification Criteria ◽  
Systemic Lupus ◽  
Acr Criteria

Background:Recently developed EULAR/ACR classification criteria for systemic lupus erythematosus (SLE) have important differences compared to the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria and the revised 1997 American College of Rheumatology (ACR) criteria: The obligatory entry criterion of antinuclear antibody (ANA) positivity is introduced and a “weighted” approach is used1. Sensitivity and specificity of these three criteria have been debated and may vary in different populations and clinical settings.Objectives:We aim to compare the performances of three criteria sets/rules in a large cohort of patients and relevant diseased controls from a reference center with dedicated clinics for SLE and other autoimmune/inflammatory connective tissue diseases from Turkey.Methods:We reviewed the medical records of SLE patients and diseased controls for clinical and laboratory features relevant to all sets of criteria. Criteria sets/rules were analysed based on sensitivity, positive predictive value, specificity and negative predictive value, using clinical diagnosis with at least 6 months of follow-up as the gold standard. A subgroup analysis was performed in ANA positive patients for both SLE patients and diseased controls. SLE patients that did not fulfil 2012 SLICC criteria and 2019 EULAR/ACR criteria and diseased controls that fulfilled these criteria were evaluated.Results:A total of 392 SLE patients and 294 non-SLE diseased controls (48 undifferentiated connective tissue disease, 51 Sjögren’s syndrome, 43 idiopathic inflammatory myopathy, 50 systemic sclerosis, 52 primary antiphospholipid syndrome, 15 rheumatoid arthritis, 15 psoriatic arthritis and 20 ANCA associated vasculitis) were included into the study. Hundred and fourteen patients (16.6%) were ANA negative.Sensitivity was more than 90% for 2012 SLICC criteria and 2019 EULAR/ACR criteria and positive predictive value was more than 90% for all three criteria (Table 1). Specificity was the highest for 1997 ACR criteria. Negative predictive value was 76.9% for ACR criteria, 88.4% for SLICC criteria and 91.7% for EULAR/ACR criteria.In only ANA positive patients, sensitivity was 79.6% for 1997 ACR criteria, 92.2% for 2012 SLICC criteria and 96.1% for 2019 EULAR/ACR criteria. Specificity was 92.6% for ACR criteria, 87.8% for SLICC criteria 85.2% for EULAR/ACR criteria.Eleven clinically diagnosed SLE patients had insufficient number of items for both 2012 SLICC and 2019 EULAR/ACR criteria. Both criteria were fulfilled by 16 diseased controls: 9 with Sjögren’s syndrome, 5 with antiphospholipid syndrome, one with dermatomyositis and one with systemic sclerosis.Table 1.Sensitivity, positive predictive value, specificity and negative predictive value of 1997 ACR, 2012 SLICC and 2019 EULAR/ACR classification criteriaSLE (+)SLE (-)Sensitivity (%)Positive Predictive Value (%)Specificity (%)Negative Predictive Value (%)1997 ACR(+) 308(-) 841527978.695.494.976.92012 SLICC(+) 357(-) 352626891.193.291.288.42019 EULAR/ACR(+) 368(-) 242826693.892.990.591.7Conclusion:In this cohort, although all three criteria have sufficient specificity, sensitivity and negative predictive value of 1997 ACR criteria are the lowest. Overall, 2019 EULAR/ACR and 2012 SLICC criteria have a comparable performance, but if only ANA positive cases and controls are analysed, the specificity of both criteria decrease to less than 90%. Some SLE patients with a clinical diagnosis lacked sufficient number of criteria. Mostly, patients with Sjögren’s syndrome or antiphospholipid syndrome are prone to misclassification by both recent criteria.References:[1]Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis 2019;78:1151-1159.Disclosure of Interests:None declared

scholarly journals Disease activity index is associated with subclinical atherosclerosis in childhood-onset systemic lupus erythematosus

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Priscila B. S. Medeiros ◽  
Roberta G. Salomão ◽  
Sara R. Teixeira ◽  
Diane M. Rassi ◽  
Luciana Rodrigues ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Subclinical Atherosclerosis ◽  
Disease Activity Index ◽  
Uncontrolled Hypertension ◽  
Childhood Onset ◽  
Systemic Lupus

Abstract Background Systemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT. Methods Cross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression. Results Twenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables. Conclusion Subclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.

scholarly journals POS0744 A NEGATIVE INTERFERON BIOMARKER CD169 / SIGLEC-1 RULES OUT SYSTEMIC LUPUS ERYTHEMATOSUS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 623.2-624
Author(s):  
L. Zorn-Pauly ◽  
A. S. L. Von Stuckrad ◽  
J. Klotsche ◽  
T. Rose ◽  
T. Kallinich ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Sialic Acid ◽  
Lupus Erythematosus ◽  
Predictive Value ◽  
Classification Criteria ◽  
Initial Diagnosis ◽  
Type I ◽  
Systemic Lupus ◽  
Potential Biomarker ◽  
Sialic Acid Binding

Background:While there have been advances in the therapy of systemic lupus erythematosus (SLE) in recent years, there have been no major new findings in SLE biomarkers [1, 2]. Type I interferon (IFN) plays a pivotal role in the pathogenesis of SLE [3]. In 2008, we first described CD169 / SIGLEC-1 (sialic acid-binding immunoglobulin-like lectin-1), an interferon-induced adhesion molecule on monocytes in SLE patients [4]. For over five years SIGLEC-1 has been routinely assessed in our clinic.Objectives:To evaluate and compare the diagnostic utility of the type I IFN induced SIGLEC-1 with established biomarkers in the initial diagnosis of the disease.Methods:We analyzed retrospectively 232 patients who were on suspicion of SLE at Charité University Hospital Berlin between October 2015 and September 2020. Patients underwent full clinical characterization, and biomarkers were determined in the routine laboratory. Based on the final diagnosis, we divided patients into two groups: A) initial diagnosis of SLE and B) Non-SLE mimicking condition.Results:In 76 patients (32.3 %) SLE was confirmed by fulfilling the EULAR / ACR 2019 classification criteria [5]. SIGLEC-1 was dramatically increased in patients with an initial diagnosis of SLE compared to patients without SLE (p<0.0001). For a threshold of 2500 molecule per monocyte, a sensitivity of 98.7 %, a specificity of 82.1 %, a negative predictive value (NPV) of 99.2 %, and a positive predictive value (PPV) of 72.8 % were calculated for SIGLEC-1. Adjusted to the prevalence of SLE in Germany (36.7 per 100,000 inhabitants [6]) NPV and PPV turned out to > 99.9 % and 0.2 %. We further aimed to compare not only the performance of the tests at a given cutoff but also across all possible measured values. Therefore, we conducted ROC curves analyses (see figure 1). The area under the curve (AUC) of SIGLEC-1 test was significantly higher than that of ANA test (AUC=0.88, p=0.031), C3 (AUC = 0.83, p=0.001), C4 (AUC=0.83, p=0.002), but not than that of the Anti-dsDNA ELISA (AUC=0.90, p=0.163).Conclusion:Our study shows that IFN activity is a hallmark at the onset of the disease and that the interferon biomarker SIGLEC-1 is valuable to rule out SLE in suspected cases.References:[1]Ostendorf L, Burns M, Durek P, Heinz GA, Heinrich F, Garantziotis P, Enghard P, Richter U, Biesen R, Schneider U et al: Targeting CD38 with Daratumumab in Refractory Systemic Lupus Erythematosus. N Engl J Med 2020, 383(12):1149-1155.[2]Furie R, Rovin BH, Houssiau F, Malvar A, Teng YKO, Contreras G, Amoura Z, Yu X, Mok CC, Santiago MB et al: Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis. N Engl J Med 2020, 383(12):1117-1128.[3]Ronnblom L, Leonard D: Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci Med 2019, 6(1):e000270.[4]Biesen R, Demir C, Barkhudarova F, Grun JR, Steinbrich-Zollner M, Backhaus M, Haupl T, Rudwaleit M, Riemekasten G, Radbruch A et al: Sialic acid-binding Ig-like lectin 1 expression in inflammatory and resident monocytes is a potential biomarker for monitoring disease activity and success of therapy in systemic lupus erythematosus. Arthritis Rheum 2008, 58(4):1136-1145.[5]Aringer M, Costenbader K, Daikh D, Brinks R, Mosca M, Ramsey-Goldman R, Smolen JS, Wofsy D, Boumpas DT, Kamen DL et al: 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Annals of the Rheumatic Diseases 2019, 78(9):1151-1159.[6]Brinks R, Fischer-Betz R, Sander O, Richter JG, Chehab G, Schneider M: Age-specific prevalence of diagnosed systemic lupus erythematosus in Germany 2002 and projection to 2030. Lupus 2014, 23(13):1407-1411.Disclosure 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.

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