Events In Systemic Lupus Erythematosus Research Articles

Cardiovascular Events in Systemic Lupus Erythematosus: A Nationwide Study in Spain From the RELESSER Registry.

This article estimates the frequency of cardiovascular (CV) events that occurred after diagnosis in a large Spanish cohort of patients with systemic lupus erythematosus (SLE) and investigates the main risk factors for atherosclerosis.RELESSER is a nationwide multicenter, hospital-based registry of SLE patients. This is a cross-sectional study. Demographic and clinical variables, the presence of traditional risk factors, and CV events were collected. A CV event was defined as a myocardial infarction, angina, stroke, and/or peripheral artery disease. Multiple logistic regression analysis was performed to investigate the possible risk factors for atherosclerosis.From 2011 to 2012, 3658 SLE patients were enrolled. Of these, 374 (10.9%) patients suffered at least a CV event. In 269 (7.4%) patients, the CV events occurred after SLE diagnosis (86.2% women, median [interquartile range] age 54.9 years [43.2–66.1], and SLE duration of 212.0 months [120.8–289.0]). Strokes (5.7%) were the most frequent CV event, followed by ischemic heart disease (3.8%) and peripheral artery disease (2.2%). Multivariate analysis identified age (odds ratio [95% confidence interval], 1.03 [1.02–1.04]), hypertension (1.71 [1.20–2.44]), smoking (1.48 [1.06–2.07]), diabetes (2.2 [1.32–3.74]), dyslipidemia (2.18 [1.54–3.09]), neurolupus (2.42 [1.56–3.75]), valvulopathy (2.44 [1.34–4.26]), serositis (1.54 [1.09–2.18]), antiphospholipid antibodies (1.57 [1.13–2.17]), low complement (1.81 [1.12–2.93]), and azathioprine (1.47 [1.04–2.07]) as risk factors for CV events.We have confirmed that SLE patients suffer a high prevalence of premature CV disease. Both traditional and nontraditional risk factors contribute to this higher prevalence. Although it needs to be verified with future studies, our study also shows—for the first time—an association between diabetes and CV events in SLE patients.

Type I interferons promote lupus through disruption of the lymphotoxin receptor-mediated mechanosensing MKL1 pathway in marginal zone macrophages (BA4P.124)

Abstract Defective clearance of apoptotic cells (ACs) is a central pathogenic event in systemic lupus erythematosus (SLE). Here, we describe an underlying mechanism in which follicular translocation of marginal zone (MZ) B cells in the spleen of lupus BXD2 mice disrupts marginal zone macrophages (MZMs), which normally clear apoptotic debris and prevent entry of the AC antigens (AC-Ags) into the follicles. The phagocytosis of ACs by the spleen MZMs is enabled by a megakaryoblastic leukemia 1 (MKL1) transcription factor-mediated mechanosensing pathway. The MZ B cells maintain this pathway through their expression of membrane lymphotoxin-α1β2 (mLT). Follicular shuttling of mLT+ MZ B cells disengages their interaction with the LTβR+ MZMs, thereby downregulating MKL1 in the MZMs. This leads to defective F-actin polymerization, loss of their ability to clear ACs and eventually MZM dissipation. Type I interferon (IFN) signaling, a well-established clinical characteristic of SLE and is commonly considered as a downstream event of AC-Ag stimulation, is identified to play a key role in MZM erosion via promoting follicular shuttling of mLT+ B cells. Follicular translocation of MZ B cells, erosion of MZMs and loss of MKL1 were similarly identified in lupus B6.Sle1.Sle2.Sle3 mouse and human SLE spleens. Collectively, the results suggest that lupus might be interrupted by strategies that maintain or enhance mechanosensing signals in the MZM barrier to prevent follicular entry of AC-Ags.

Therapeutic effects of the artemisinin analog SM934 on lupus-prone MRL/lpr mice via inhibition of TLR-triggered B-cell activation and plasma cell formation.

We previously reported that SM934, a water-soluble artemisinin derivative, was a viable treatment in murine lupus models. In the current study, we further investigated the therapeutic effects of a modified dosage regimen of SM934 on lupus-prone MRL/lpr mice and explored its effects on B cell responses, a central pathogenic event in systemic lupus erythematosus (SLE). When orally administered twice-daily, SM934 significantly prolonged the life-span of MRL/lpr mice, ameliorated the lymphadenopathy symptoms and decreased the levels of serum anti-nuclear antibodies (ANAs) and of the pathogenic cytokines IL-6, IL-10 and IL-21. Furthermore, SM934 treatment restored the B-cell compartment in the spleen of MRL/lpr mice by increasing quiescent B cell numbers, maintaining germinal center B-cell numbers, decreasing activated B cell numbers and reducing plasma cell (PC) numbers. Ex vivo, SM934 suppressed the Toll-like receptor (TLR)-triggered activation and proliferation of B cells, as well as antibody secretion. Moreover, the present study demonstrated that SM934 interfered with the B-cell intrinsic pathway by downregulating TLR7/9 mRNA expression, MyD88 protein expression and NF-κB phosphorylation. In human peripheral blood mononuclear cells (PBMCs), consistent with the results in MRL/lpr mice, SM934 inhibited TLR-associated B-cell activation and PC differentiation. In conclusion, a twice daily dosing regimen of SM934 had therapeutic effects on lupus-prone MRL/lpr mice by suppressing B cell activation and plasma cell formation.

Physical Activity Program Is Helpful for Improving Quality of Life in Patients with Systemic Lupus Erythematosus.

Given the crucial events in systemic lupus erythematosus (SLE) such as joint and muscle pain, fatigue, depression, obesity and osteoporosis, the very thought of exercising can be challenging. This prospective study included 60 patients diagnosed with SLE in stable condition. A randomly selected group of 30 women had aerobic training on a bicycle ergometer for a period of 15 minutes, 3 times per week for 6 weeks, while the second group of 30 women performed isotonic exercises (to stretch and lengthen muscles and improve the range of motion) for 30 minutes, 3 times per week during the same period. Fatigue Severity Scale (FSS), Short Form 36 (SF36) questionnaire on the quality of life and Beck depression inventory (BDI) were analyzed at baseline and after 6 weeks. At baseline FSS score was 53.8 ± 5.7 and after the physical activity FSS score was 29.1 ± 7.8 (FSS ≥ 36; fatigue is present). The largest number of patients (66.7%) was in a moderate depressed state at the baseline, while after physical activities 61.7% of patients, had a mild mood disturbance. There were significant differences (p < 0.001) in values of all areas of quality of life questionnaire SF36 before and after the implementation of physical activity. The type of physical activity had no influence in FSS and BDI values. Continuous physical activity, regardless of its type, significantly improved quality of life of SLE patients. We recommend regular physical activity as an integral part of modern therapeutic approach in this patient population.

Development and validation of a new algorithm for attribution of neuropsychiatric events in systemic lupus erythematosus.

The aim of this study was to develop and validate an algorithm to assist the attribution of neuropsychiatric (NP) events to underlying disease in SLE patients. Phase 1 identified and categorized candidate items to be included in the algorithm for the attribution of an NP event to SLE and their relative weights through a literature-informed consensus-driven process. Using a retrospective training cohort of SLE, phase 2 validated items selected in phase 1 and refined weights through a data-driven process, fitting items as independent variables and expert evaluation (clinical judgement) as reference standard in logistic models. Phase 3 consisted of a validation process using an external multicentre retrospective SLE cohort. Phase 1 identified four different items: timing of the NP event, type of event, confounding factors and favouring factors. The training and validating cohorts included 228 and 221 patients, respectively. Each patient experienced at least one NP event characterized using the ACR case definition. In these samples, items selected in phase 1 showed good performance in discriminating patients with NPSLE: the area under the receiver operating characteristic curve using dichotomous outcomes was 0.87 in the training set and 0.82 in the validating set. Relevant cut-offs of the validated score identify events with a positive predictive value of 100% (95% CI 93.2, 100) and 86.3% (95% CI 76.2, 93.2) in the training and validating cohorts, respectively. A new algorithm based on a probability score was developed and validated to determine the relationship between NP events and SLE.

Predictors of cardiovascular events in patients with systemic lupus erythematosus (SLE): a systematic review and meta-analysis.

Cardiovascular disease represents an important cause of morbidity and mortality in patients with a diagnosis of systemic lupus erythematosus (SLE), due to a complex interplay between traditional risk factors and disregulation of autoimmunity but uncertainty is still present about the most important predictors of cardiovascular events. The aim of our work was to perform a collaborative systematic review on the main predictors of cardiovascular events in SLE patients. PubMed and Cochrane were systematically searched for eligible studies on SLE and cardiovascular events between January 2008 and December 2012. Study features, patient characteristics and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate - 95% confidence intervals) and consistency of predictors was formally appraised. A total of 17,187 patients was included; of those, 93.1% were female and the median age was 39years. After a median follow-up period of 8 years, cardiovascular events presented in 25.4%, including acute myocardial infarction (4.1%) and stroke (7.3%). The most important predictors may be divided into traditional risk factors, such as male gender (OR 6.2, CI 95% 1.49-25), hyperlipidaemia (OR 3.9, CI 95% 1.57-9.71), familiar history of cardiac disease (OR 3.6, CI 95% 1.15-11.32) and hypertension (OR 3.5, CI 95% 1.65-7.54), and SLE-related features, such as the presence of auto-antibodies (OR 5.8 and 5.0, CI 95% 3.28-7.78) and neurological disorders (OR 5.2, CI 95% 2.0-13.9). A low correlation was shown for the importance of organ damage and SLE activity (respectively OR 1.4, CI 95% 1.09-4.44 and OR 1.2, CI 95% 1.2-1.2), as well as for age at diagnosis (OR 1.1, CI 95% 1.07-1.17). Cardiovascular events in SLE patients are caused by a multifactorial mechanism, including both traditional and disease-specific risk factors. A global valuation with an individual risk stratification based on both these features is important to correctly manage these patients in order to reduce negative outcomes.

Cigarette smoking, antiphospholipid antibodies and vascular events in Systemic Lupus Erythematosus

ObjectiveSmoking can induce autoantibodies in persons who are genetically predisposed to rheumatoid arthritis. We investigated the association between smoking and antiphospholipid antibodies (aPL) in systemic lupus erythematosus (SLE), a question...

AB0675 Cardiovascular risk assessment in systemic lupus erythematosus patients using the south european and spanish score charts

BackgroundSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease with increased risk for accelerated atherosclerosis and coronary artery disease. SLE patients have a bimodal mortality pattern, the later one being...

Superficial vein thrombosis, thrombin generation and activated protein C resistance as predictors of thromboembolic events in lupus and antiphospholipid patients. A prospective cohort study

IntroductionPredicting thrombosis in patients with systemic lupus erythematosus (SLE) and/or antiphospholipid antibodies (aPL) is still challenging. Our objective was to determine risk factors for thrombotic events including activated protein C (APC) resistance proven by a thrombin generation (TG) assay in patients with SLE and/or aPL. Materials and methodsWe performed a prospective cohort study in a French University Hospital and tertiary care center. Ninety-two consecutive patients with SLE and/or aPL without ongoing anticoagulant treatment were enrolled. The outcome was time to thrombotic event. We evaluated clinical and laboratory variables including APC sensitivity ratio (APCsr) determined by TG. An APCsr>90th percentile of a control population indicated APC resistance. ResultsPatients were followed-up for a median duration of 35months (inter-quartile range: 26 to 62; 320 patient-years). Thrombosis during follow-up occurred in 18 patients. In univariate analysis, together with history of hypertension, superficial vein thrombosis (SVT) and arterial thrombosis, patients with both aPL and APC resistance had an increased risk for incident thromboembolic events (HR, 3.67[95% confidence interval, 1.31 to 10.31]). In multivariate analysis, only history of hypertension (HR, 10.77 [95% confidence interval, 3.15 to 36.83]), SVT (HR, 7.45 [95% confidence interval, 2.25 to 24.66]) and arterial thrombosis (HR, 3.31 [95% confidence interval, 1.14 to 9.55]) remained independent risk factors. ConclusionsHistory of thrombosis including seemingly benign SVT have a higher predictive value for incident thrombotic events in SLE or aPL patients than APC resistance proven by TG.

Contact activation products are new potential biomarkers to evaluate the risk of thrombotic events in systemic lupus erythematosus

IntroductionPatients with systemic lupus erythematosus (SLE) have persistent platelet activation and an increased risk of thrombotic events, which cannot be accounted for by traditional cardiovascular risk factors. Factor (F)XII has a potentially important role in thrombus formation and is triggered by activated platelets. We therefore asked whether the contact system is involved in inflammation and vascular disease (VD) in SLE.MethodsFibrin clots were incubated with purified FXII or whole blood, and the activation and regulation of FXII were studied. Plasma from SLE patients with (n = 31) or without (n = 38) previous VD and from matched healthy controls (n = 68) were analyzed for the presence of complexes formed between contact system enzymes and antithrombin (AT) or C1 inhibitor (C1INH) and evaluated with regard to clinical data and laboratory parameters.ResultsFibrin clots elicited FXII activation and acted as co-factors for AT. In clotting plasma, the levels of FXIIa-AT increased, and FXIIa-C1INH decreased. A similar reciprocal relationship existed in SLE patients. FXIIa-AT was elevated in the SLE patients with a history of VD, while the corresponding levels of factor FXIIa-C1INH were significantly decreased. FXIIa-AT correlated strongly with platelet parameters. The odds ratio for VD among the SLE patients was 8.9 if they had low levels of FXIIa-C1INH, 6.1 for those with high levels of FXIIa-AT, and increased to 23.4 for those with both decreased levels of FXIIa-C1INH and increased levels of FXIIa-AT.ConclusionsActivation of FXII is elicited by fibrin during thrombotic reactions in vitro and in vivo, and fibrin acts as a heparin-like co-factor and regulates AT. Patients with SLE had altered levels of FXIIa-serpin complexes, supporting that the contact system is involved in this disease. FXIIa-serpin complexes are strongly associated with previous VD in SLE patients, suggesting that these complexes are potential biomarkers for monitoring and assessing the risk of thrombotic events in SLE.

HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus

Background and objectivesVascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class...

Factors and comorbidities associated with first neuropsychiatric event in systemic lupus erythematosus: does a risk profile exist? A large multicentre retrospective cross-sectional study on 959 Italian patients

To analyse risk factors and comorbidities potentially associated with CNS involvement in a large cohort of Italian patients affected by SLE. A number of generic (not strictly SLE related) and specific (disease related) risk factors to which all patients have been exposed in the span of 5 years before the first neuropsychiatric (NP) event or before the last available observation were checked for and their distribution was analysed in 959 SLE patients with and without NP involvement; all the first NP events that occurred in a time frame of 10 years were recorded and categorized as SLE related or SLE unrelated. Three hundred and twenty-six SLE patients with and 633 SLE patients without NP manifestations were included in the study. A total of 469 NP events were recorded. Headache (26.1%), cerebrovascular events (22.7%), mood disorders (8.9%), seizures (14.4%) and cognitive dysfunctions (9.5%) were the most frequent SLE-related NP events. More risk factors [mean 4.52 (2.44) vs 3.73 (2.01); P < 0.0001] were observed in patients with than without NP involvement. Overall, aPLs, LA and APS were factors more strongly associated with NP involvement. In SLE, NP involvement and aPLs were confirmed as closely related. Furthermore, other modifiable generic risk factors, such as hypertension, carotid vasculopathy and dyslipidaemia, appeared to be related to the occurrence of cerebral vascular accident (CVA) and cognitive dysfunctions, suggesting the need for a more intensive preventive strategy to optimize the management of NP lupus.

Cardiovascular event in systemic lupus erythematosus in northern Sweden: Incidence and predictors in a 7-year follow-up study

An increased rate of cardiovascular disease (CVD) has been suggested in patients with systemic lupus erythematosus (SLE). The risk for myocardial infarction (MI), coronary artery disease and stroke has been reported as particularly prevalent in younger females compared with the reference population. This study was performed to analyse the standard incidence ratio (SIR) of and predictors for cardiovascular events (CVEs) in patients with SLE from northern Sweden, with a fairly homogenous population. In 2000 all prevalent patients with SLE (≥4 American College of Rheumatology [ACR] criteria; n = 277) from the four northern-most counties of Sweden were assessed with clinical and laboratory analyses. Seven years follow-up data concerning MI and stroke were extracted from the national registers of hospitalization and death in Sweden. The incidence ratio among the patients was compared with that for the general population from the same catchment area using data from the same register and Statistics Sweden. To identify time to event and CVE predictors, two matched controls for each patient were used and disease related variables as CVD predictors. The SIR for a CVE was 1.27 (95% CI 0.82-1.87) and for females separately aged 40-49 years was 8.00 (95% CI 1.65-23.38). The overall SIR for MI was 2.31 (95% CI 1.34-3.7), for females overall was 1.75 (95% CI 0.84-3.22) and for females aged between 40 and 49 years was 8.7 (95% CI 1.1-31.4). The time to an event was significantly shorter among SLE patients (p < 0.001) and was predicted by hypertension adjusted for smoking and disease. High SLEDAI and anti-cardiolipin IgG antibodies predicted an event in Cox proportional hazards regression models adjusted for age and previous MI. Diabetes, smoking ever and sex did not affect the prediction models. The risk of a CVE, or MI, was eight- or nine-fold greater among middle-aged female SLE patients. Time to event was significantly shorter and CVE was associated with SLE-related factors including hypertension and age.

PND12 the Cost of Corticosteroid-associated Adverse Events in Systemic Lupus Erythematosus

PND12 the Cost of Corticosteroid-associated Adverse Events in Systemic Lupus Erythematosus

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

ObjectiveNeuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to...

Enhanced Phosphoinositide 3-Kinase δ Activity Is a Frequent Event in Systemic Lupus Erythematosus That Confers Resistance to Activation-Induced T Cell Death

Systemic lupus erythematosus (SLE) is a human chronic inflammatory disease caused by the action of autoreactive T and B cells. Class I phosphoinositide-3-kinases (PI3K) are enzymes that trigger formation of 3-poly-phosphoinositides that induce cell survival. Enhanced PI3K activation is a frequent event in human cancer. Nonetheless, in a genetic model with enhanced activation of class I(A) PI3K in T cells, mice show a greater tumor index but die of a lupus-like disease. In this study, we studied the potential PI3K involvement in human SLE. The PI3K pathway was frequently activated in SLE patient PBMC and T cells (∼70% of cases), more markedly in active disease phases. We examined the mechanism for PI3K pathway activation and found enhanced activation of PI3Kδ in SLE peripheral blood T cells. The magnitude of PI3K pathway activation in patients paralleled activated/memory T cell accumulation. We examined potential tolerance mechanisms affected by increased PI3K activity; SLE patients showed reduced activation-induced cell death of activated/memory T cells. Moreover, the defective activation-induced cell death in SLE T cells was corrected after reduction of PI3Kδ activity, suggesting that PI3Kδ contributes to induction of enhanced SLE memory T cell survival. These observations point to PI3Kδ as a target of clinical interest for SLE.

SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus

ObjectiveTo examine change in health-related quality of life in association with clinical outcomes of neuropsychiatric events in systemic lupus erythematosus (SLE).MethodsAn international study evaluated newly diagnosed SLE patients for neuropsychiatric...

SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus

SF-36 summary and subscale scores are reliable outcomes of neuropsychiatric events in systemic lupus erythematosus

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus

Endocardite de Libman-Sacks, anticorpos antifosfolípides e trombose arterial no lúpus ertitematoso sistêmico: relato de caso

Case report of a 38-year-old female patient with systemic lupus erythematosus (SLE) who presented an acute arterial thromboembolic event in the right lower limb. Investigation showed the presence of antiphospholipid antibodies and sterile vegetation in the mitral valve, Libman-Sacks endocarditis (LSE). Possible causes of thromboembolic events in SLE are discussed, with emphasis on current recommendations for diagnosis and treatment of LSE.