Systemic Lupus Erythematosus Damage Research Articles

Predictors of corticosteroid tapering in SLE patients: the Hopkins Lupus Cohort

Organ damage in systemic lupus erythematosus (SLE) patients is highly associated with the use of corticosteroids. Doses of prednisone below 6 mg daily are associated with reduced organ damage. We now report on the largest prospective cohort study of predictors of prednisone tapering in SLE patients. A total of 866 SLE patients (91% female, 50% Caucasian, 43% African-American, mean age 43 years) who consented for the Hopkins Lupus Cohort from 1987 through 2009 were included. The analysis was based on patient visits in which the previously prescribed dose of prednisone was 5 mg/day. We then examined the proportion of times the patient's dose was reduced to below 5 mg/day ("tapering"). Among those patients who tapered and were followed for at least one year thereafter, we examined the proportion whose prednisone dose remained below 5 mg/day for at least one year ("Successful tapering"). Rates of tapering and successful tapering were calculated for patient subsets based on demographic and clinical characteristics. The analyses showed that Caucasians, younger patients, patients with a higher level of education, lower disease activity, or absence of urine protein were more likely to have a prednisone taper. However, successful tapering was not dependent on age, ethnicity, or education. As expected, successful tapering was more frequent in those with lower disease activity. Successful tapering was achieved more often after the year 2000. Our study suggests that successful tapering of prednisone below 5 mg has increased since the year 2000, which may reflect the greater knowledge of the long-term harm of even low-dose chronic corticosteroid use. Caucasians, younger age, higher level of education, and absence of proteinuria predicted tapering, but not successful tapering. Ongoing cutaneous or arthritis activity were associated with unsuccessful tapering. Lack of disease activity, as expected, was the only major clinical variable that significantly predicted successful tapering.

ADAMTS-13 metalloprotease abnormalities in systemic lupus erythematosus: is there a correlation with disease status?

To clarify the role of ADAMTS-13 in the pathogenesis of thrombotic microangiopathy in systemic lupus erythematosus (SLE) we evaluated ADAMTS-13 profile (metalloprotease antigen levels, anti-ADAMTS-13 autoantibody levels, activity) in distinct patient groups according to disease activity, extent of cumulative tissue damage and history of antiphospholipid syndrome or end-organ damage. Forty-one lupus patients were analysed. ADAMTS-13 metalloprotease antigen levels and anti-ADAMTS-13 autoantibodies were evaluated by ELISA. ADAMTS-13 activity was measured by Fluorescence resonance energy transfer (FRET) technique. ADAMTS-13 metalloprotease antigen levels were significantly decreased in patients with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) >1 (p<0.05). ADAMTS-13 metalloprotease antigen levels also exhibited a significant inverse correlation with anti-dsDNA levels (r= -0.60, p<0.05). Anti-ADAMTS-13 autoantibodies were marginally higher in patients with positive anti-dsDNA (p=0.08). Additionally, patients with positive anti-ADAMTS-13 autoantibodies exhibited the lowest activity levels (p<0.05). To our knowledge ADAMTS-13 profile in SLE has not been studied in regard to composite structured indices. The results of this study suggest that in patients with active SLE or considerable cumulative tissue damage, ADAMTS-13 levels may be decreased and anti-ADAMTS-13 autoantibodies may partially mediate this reduction. Further evaluation of ADAMTS-13 profile may explain its role in the pathogenesis of thrombotic microangiopathy in lupus patients and reveal a potential prognostic marker of microthrombotic manifestations in SLE.

High‐sensitivity C‐reactive protein, disease activity, and cardiovascular risk factors in systemic lupus erythematosus

To study the level of high-sensitivity C-reactive protein (hsCRP) and its relationship with disease activity, damage, and cardiovascular risk factors in patients with systemic lupus erythematosus (SLE). Consecutive patients who fulfilled ≥4 American College of Rheumatology criteria for SLE who did not have a concurrent infection were recruited. Blood was assayed for hsCRP level, and disease activity, organ damage of SLE, and cardiovascular risk factors were assessed. Linear regression analyses were performed for the relationship between hsCRP levels, SLE activity, damage, and cardiovascular risk factors. In total, 289 patients were studied (94% women, mean ± SD age 39.0 ± 13.1 years, and mean ± SD SLE duration 7.8 ± 6.7 years). The mean ± SD Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 4.9 ± 5.6 and clinically active SLE was present in 122 patients (42%). The mean ± SD hsCRP level was 4.87 ± 12.7 mg/liter, and 28 patients with active SLE (23%) had an undetectable hsCRP level (<0.3 mg/liter). The linear regression analyses revealed a significant correlation between hsCRP level and musculoskeletal disease (β = 0.21), hematologic disease (β = 0.19), active serositis (β = 0.46), and clinical SLEDAI score (β = 0.24) after adjusting for age, sex, body mass index, serum creatinine, and the use of various medications (P < 0.005 for all). hsCRP levels correlated significantly with anti-double-stranded DNA titer (β = 0.33, P < 0.001) but did not correlate with complement C3 (β = -0.07, P = 0.26). An hsCRP level >3 mg/liter was significantly associated with male sex, long-term smoking, diabetes mellitus, a higher atherogenic index, and a history of arterial thrombosis. hsCRP levels correlated significantly with pulmonary and endocrine damage scores. hsCRP was detectable in 77% of SLE patients with clinically active disease and correlated with SLEDAI scores, particularly in serositis and in the musculoskeletal and hematologic systems. Elevated hsCRP levels in SLE were associated with certain cardiovascular risk factors and a history of arterial thromboembolism.

Neuropsychiatric damage in Systemic Lupus Erythematosus: Possible protective role of medications.

Objective: To examine the possible role of medications in the occurrence of neuropsychiatric damage in patientswith systemic lupus erythematosus (SLE). Material and methods: SLE patients from the LUMINA (Lupus inMinorities: Nature vs. Nurture) cohort (ACR criteria, ≥ 16 years of age at enrollment and ≤5 years of diseaseduration) were studied. Time-to-neuropsychiatric damage [defined according with the Systemic Lupus CollaboratingClinics (SLICC) Damage Index (SDI): neurocognitive impairment or psychosis, seizures, cranial or peripheralneuropathy, stroke or surgical resection not due to malignancies and transverse myelitis] was examined by univariableand multivariable Cox regression analyses. Propensity score analyses were done to further determine the possibleprotective role of hydroxychloroquine in neuropsychiatric damage occurrence. Results: Six-hundred and thirtytwopatients were studied. Age, Caucasian ethnicity, disease activity over time, diabetes and abnormal illness-relatedbehaviors were associated with a shorter time-to-the occurrence of neuropsychiatric damage whereas photosensitivity,anemia, Raynaud’s phenomenon, hydroxychloroquine and a medium dose of prednisone were associated with alonger time. Although the direction of the association remained the same by propensity score analyses(hydroxychloroquine), significance was no longer evident. Conclusions: Our data suggest a possible protectiverole of hydroxychloroquine and moderate doses of prednisone in the occurrence of neuropsychiatric damage inpatients with SLE. (Rev. Neuropsiquiatría 2008; 71: 51-57).

Interferon α impairs survival and function of circulating angiogenic cells in vitro: a model of failed endothelial repair in systemic lupus erythematosus

BackgroundPatients with systemic lupus erythematosus have an increased risk of cardiovascular disease. Interferon α may impair endothelial repair mechanisms in lupus. Patients with systemic lupus erythematosus have fewer circulating angiogenic cells (CAC) and endothelial progenitor cells (EPCs). Mixed EPC and CAC populations have been shown to be sensitive to interferon α (IFNα). We aimed to investigate the effects of IFNα2b on an in-vitro model of angiogenesis and vascular repair. MethodsPeripheral blood mononuclear cells from healthy individuals were cultured on human fibronectin for 7 days. CAC phenotype was confirmed by low-density lipoprotein (LDL) uptake, lectin binding, and cell surface marker expression by RT-PCR. Cell survival in response to IFNα2b (0·01–10 ng/mL) was determined by the number of LDL-uptake-positive cells. To study CAC function, supernatant from CACs in the presence or absence of 10ng/mL IFNα2b was added to human aortic endothelial cells on Matrigel. Tubule formation was assessed at 14 h. FindingsCACs expressed markers of endothelial (CD31) and myeloid lineage (CD14, CD45), and strongly expressed the markers CD68, CD163, and CD206 suggesting an alternatively activated (M2) macrophage phenotype. IFNα2b significantly reduced the number of CACs at day 7 in a dose-dependent manner (r2= −0·769, p<0·0001). In co-culture with endothelial cells on Matrigel, CACs co-localised to the endothelial tubules but did not form tubule networks alone. CAC supernatant significantly increased tubule network density in terms of total pixel area (mean 27 781 [SE 1469] vs 36 283 [1804], p=0·0065), number of branches (340·2 [11·0] vs 510·6 [70·2], p=0·0434), junctions (162·4 [5·9 vs 241·1 [28·0], p=0·0104), and closed loops (21·8 [1·9] vs 38·3 [2·2], p=0·005). IFNα2b significantly reduced the number of closed loops (38·2 [2·2] vs 24·1 [3·5], p=0·0094). All other network parameters were reduced by IFNα2b but did not reach statistical significance. InterpretationCACs are of myeloid lineage, and CAC supernatant contains potent angiogenic factors which augment endothelial tubule networks. IFNα2b dramatically reduces the survival of CACs in vitro, resulting in reduced tubule network formation and may be a mechanism by which IFNα promotes vascular damage in systemic lupus erythematosus. FundingNorth West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics.

Cross-cultural validation of a disease-specific patient-reported outcome measure for lupus in Philippines

LupusPRO is a disease-targeted patient-reported outcome measure that was developed and validated among US patients with systemic lupus erythematosus (SLE). We report the cross-cultural validation results of the LupusPRO English-language version among Filipino SLE patients. The 43-item LupusPRO was pretested in 15 SLE individuals, then administered to 106 SLE patients, along with short-form SF36 and the EQ5D visual analogue scale. A mail/drop-back LupusPRO and change in health status item survey were returned within two to three days. Demographics, clinical and serological characteristics, disease activity and damage measured by PGA, SELENA-SLEDAI, LFA Flare, and SLICC-ACR SLE damage index (SDI) were collected. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent validity (corresponding SF36 domains) and criterion validity (against general health and disease activity measures) were tested. Reported p values are two tailed. A total of 121 Filipino SLE subjects (95% women, median age 31.0 ± 16 years) with at least a high school level of English instruction participated. Median (IQR) PGA, SLEDAI and SDI were 0.0 (1.0), 2.0 (10) and 0 (1), respectively. ICR exceeded 0.7 for all domains except the lupus symptoms domain. TRT was greater than 0.85 for all LupusPRO domains. Convergent and criterion validity were observed against corresponding SF36 domains and disease activity measures. The tool was well received by patients. Confirmatory factor analysis showed good fit. English LupusPRO has fair psychometric properties among SLE patients in the Philippines, and is now available for inclusion in clinical trials and longitudinal studies to test responsiveness to change.

Plasma levels of osteopontin identify patients at risk for organ damage in systemic lupus erythematosus

IntroductionOsteopontin (OPN) has been implicated as a mediator of Th17 regulation via type I interferon (IFN) receptor signaling and in macrophage activity at sites of tissue repair. This study assessed whether increased circulating plasma OPN (cOPN) precedes development of organ damage in pediatric systemic lupus erythematosus (pSLE) and compared it to circulating plasma neutrophil gelatinase-associated lipocalin (cNGAL), a predictor of increased SLE disease activity.MethodscOPN and cNGAL were measured in prospectively followed pSLE (n = 42) and adult SLE (aSLE; n = 23) patients and age-matched controls. Time-adjusted cumulative disease activity and disease damage were respectively assessed using adjusted-mean SLE disease activity index (SLEDAI) (AMS) and SLICC/ACR damage index (SDI).ResultsCompared to controls, elevated cOPN and cNGAL were observed in pSLE and aSLE. cNGAL preceded worsening SLEDAI by 3-6 months (P = 0.04), but was not associated with increased 6-month AMS. High baseline cOPN, which was associated with high IFNalpha activity and expression of autoantibodies to nucleic acids, positively correlated with 6-month AMS (r = 0.51 and 0.52, P = 0.001 and 0.01 in pSLE and aSLE, respectively) and was associated with SDI increase at 12 months in pSLE (P = 0.001). Risk factors for change in SDI in pSLE were cOPN (OR 7.5, 95% CI [2.9-20], P = 0.03), but not cNGAL, cumulative prednisone, disease duration, immunosuppression use, gender or ancestry using univariate and multivariate logistic regression. The area under the curve (AUC) when generating the receiver-operating characteristic (ROC) of baseline cOPN sensitivity and specificity for the indication of SLE patients with an increase of SDI over a 12 month period is 0.543 (95% CI 0.347-0.738; positive predictive value 95% and negative predictive value 38%).ConclusionHigh circulating OPN levels preceded increased cumulative disease activity and organ damage in SLE patients, especially in pSLE, and its value as a predictor of poor outcome should be further validated in large longitudinal cohorts.

Endothelial progenitor cells in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune-mediated disease, characterized by inflammation of small arteries and arterioles. Patients with SLE suffer from a 17-fold higher risk for developing atherosclerosis than healthy individuals. Endothelial progenitor cells (EPCs) have been shown to be critically involved in microvascular repair under both physiological and pathological conditions. The aim of the present study was to analyze EPC regeneration and mobilization in SLE patients with variable disease activity and undergoing different treatment regimens. Forty-eight patients with SLE were analyzed. Healthy, age- and sex-matched individuals served as controls. Total circulating EPCs were enumerated by FACS analysis, and regenerative activity of the cells was analyzed by a colony-forming assay. Vasomodulatory mediators were quantified by ELISA. SLE patients did not show lower or higher percentages of total circulating EPCs, but they displayed significantly lower colony numbers as compared with healthy controls, indicating impaired EPC regeneration and mobilization. Low and high disease activity were associated with decreased EPC regeneration, while moderate disease activity was not. Hypertension and, to some extent, renal involvement were associated with reduced colony formation. Patients not receiving hydroxychloroquine (HCQ) treatment and those undergoing glucocorticoid therapy showed impaired EPC regeneration as well. SLE patients suffer from both defective regeneration and mobilization of EPCs. Such an impairment of the EPC system, as one key regulatory element in the process of vasorepair, could potentially promote microvascular damage in SLE. Long-term glucocorticoid therapy may further suppress the EPC system, while HCQ may prevent regeneration of the cells.

Global trends, potential mechanisms and early detection of organ damage in SLE

Increased longevity of patients with systemic lupus erythematosus (SLE) leads to chronic organ damage accrual, which reduces the possibility of further survival improvement in patients with the disease. Observations from lupus centres worldwide revealed that the prevalence of damage occurring in the cardiovascular system in patients with SLE has increased over the past four decades. The results of a meta-analysis involving over 70 observational studies demonstrated that lupus-related organ damage involving the neuropsychiatric and renal systems also remains a major factor that limits survival improvement in patients with this disease. While efforts to halt acute lupus-related injury are continuing, through early diagnosis and effective use of immunosuppressive agents, a concomitant strategy to improve survival of patients with SLE would be early detection and timely treatment of lupus-related organ damage with meticulous monitoring. This Review discusses the pattern and trend of organ damage in patients with SLE worldwide, the potential serological and genetic mechanisms of organ damage, and the advances in research on potential tools for early detection of lupus-related organ damage, such as functional brain imaging techniques, measurement of endothelial function, identification of biomarkers from body fluids, and development of risk calculation models.

Predictors of organ damage in systemic lupus erythematosus: The Hopkins Lupus Cohort

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI) is the accepted measure of permanent organ damage in systemic lupus erythematosus (SLE). We analyzed data from a large SLE cohort to identify variables associated with rates of damage accrual as measured by the SDI. The study included 2,054 SLE patients (92% female, 56% white, and 37% African American) with a mean age at diagnosis of 33 years. The SDI score was calculated retrospectively at the time of cohort entry and prospectively during followup. The relationships between time-invariant patient characteristics and rates of damage accrual were assessed based on the damage score at the last available followup visit. The relationships between time-varying patient characteristics and damage accrual were assessed based on the timing of damage accrual during cohort participation. Overall, the SDI score increased at a rate of 0.13 per year. Higher rates of damage were observed for those who were older, male, or African American, had a lower income or education level, were hypertensive, were positive for lupus anticoagulant, or had proteinuria. During followup, the risk of damage was higher for those who were older, had more disease activity, had low complement levels, were positive for anti-double-stranded DNA, satisfied more ACR criteria for SLE, or were receiving corticosteroids. Lower risk was observed among patients receiving hydroxychloroquine. After adjustment for other variables, age, hypertension, and corticosteroid use emerged as the most important predictors of damage accrual. Our findings indicate that rates of damage vary in demographic subgroups, but much variation appears to be explained by hypertension and corticosteroid use. These data clearly point to the need for tight control of disease activity without reliance on corticosteroids.

Interplay of neutrophils and type I interferons in the development of end-organ damage in SLE

Patients with systemic lupus erythematosus (SLE) have up to a 50-fold increased risk of developing atherosclerotic cardiovascular disease that cannot be explained by the Framingham risk equation. While both SLE-specific and nonspecific mechanisms have been proposed to play a prominent role in the induction of premature vascular damage in this disease, the exact etiology remains unclear. We have proposed that an imbalance between vascular damage and repair probably induced by IFNα and other type I interferons could play a prominent role in the induction of accelerated atherosclerosis in SLE. Our group and others have recently elucidated the potential role that these cytokines play in the development and progression of premature atherosclerotic disease in SLE and, potentially, in other autoimmune diseases. More recently, a novel role for aberrant neutrophils in the development of autoimmune responses and vascular damage in SLE and other diseases has emerged; in particular, the role that neutrophil extracellular traps may play in the development of this disease and its vascular complications such as endothelial dysfunction and atherothrombosis. The recent description of a distinct subset of proinflammatory neutrophils isolated from lupus patients that induces vascular damage and synthesizes type I interferons has shed new light into a potentially important cell subset implicated in endothelial damage. Finally, novel discoveries pertaining to the interactions of lipoproteins and the immune system may prove quite informative in understanding how premature atherosclerotic plaque develops in lupus.

Increased Organ Damage Associated with Deterioration in Volumetric Bone Density and Bone Microarchitecture in Patients with Systemic Lupus Erythematosus on Longterm Glucocorticoid Therapy

To evaluate bone quality in patients with systemic lupus erythematosus (SLE) who were undergoing longterm glucocorticoid (GC) therapy, and to focus on the correlation between bone quality and organ damage. Seventy-eight female patients with SLE and organ damage taking longterm GC, and 72 age-matched SLE patients without damage taking longterm GC were recruited for study. Clinical variables of interest included disease activity, cumulative organ damage (by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SDI), major organ involvement (musculoskeletal damage and neuropsychiatric damage, etc.), and use of medication. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry. Bone geometry, volumetric BMD (vBMD), microarchitecture, and biomechanical properties were measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Patients were mean age of 45 years (SD 10) and 54% were postmenopausal. The median SDI score of the cohort was 1 (interquartile range 1-2, range 1-5). Compared with patients without damage, the prevalence of osteopenia at either total hip or lumbar spine was significantly higher, and there were trends of deterioration of bone geometry, vBMD, microarchitecture, and biomechanical properties in patients with organ damage. Potential risk factors for bone quality in patients with damage were screened by univariate analysis. During multiple regression analysis, SDI was the only clinical variable consistently associated with deterioration of vBMD and microarchitecture. Cumulative organ damage consistently correlated with deterioration of vBMD and bone microarchitecture in SLE patients with damage on longterm GC therapy. HR-pQCT provides an insight into the underlying mechanism of bone loss in SLE.

Response to Comment on “Inflammasome Activation of IL-18 Results in Endothelial Progenitor Cell Dysfunction in Systemic Lupus Erythematosus”

We thank Drs. Duan et al. for their comments and for summarizing the observations of several of our recent publications that focus on the putative roles of type I IFNs in the development of premature cardiovascular damage in systemic lupus erythematosus. We agree with them that additional studies

Differences in Autoantibody Profiles and Disease Activity and Damage Scores Between Childhood- and Adult-Onset Systemic Lupus Erythematosus: A Meta-Analysis

Age at systemic lupus erythematosus (SLE) onset may impact autoantibodies, disease activity, and damage. A meta-analysis of all studies that directly compared childhood-onset lupus (cSLE) to adult-onset lupus was performed to determine which autoantibodies and whether activity and damage scores vary between adult- and pediatric-onset SLE. A literature search of the MEDLINE/PubMed, EMBASE, CINAHL, and SCOPUS databases (until January 2011) was conducted to identify relevant articles. Study quality was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Two independent reviewers determined eligibility criteria. Pooled odds ratios and mean differences were calculated assuming random effects, and heterogeneity was estimated and presented as (odds ratios; 95% confidence interval). Of the 484 studies identified, 19 were eligible. The total number of patients was 7519. Mean trial quality was 18/32, ranging from 8 to 29. Several statistically significant differences were found: more frequently positive anti-dsDNA antibody (1.97; 1.31 to 2.96) and IgG/IgM anticardiolipin antibody (1.66; 1.20 to 2.28), and mean disease activity scores (SLE Disease Activity Index) (4.73; 2.13 to 7.32) were higher in cSLE. Disease damage [SLE damage index (SDI)] was lower in cSLE, but not significantly (0.50; -0.13 to 1.14). Rheumatoid factor was increased in adults (0.53; 0.32 to 0.87). The frequency of the autoantibodies and laboratories was not different between the groups (ANA, anti-Smith, anti-RNP, anti-U1RNP, anti-Ro and anti-La, antiphospholipid, lupus anticoagulant, complements, ssDNA, and Coomb's test). The results of this meta-analysis suggest that cSLE may have different autoantibody profiles (increased anti-dsDNA and anticardiolipin antibody, less rheumatoid factor), and more disease activity than adult-onset SLE. Damage may be less in children, but larger studies are needed.

Type I Interferons Are Associated with Subclinical Markers of Cardiovascular Disease in a Cohort of Systemic Lupus Erythematosus Patients

BackgroundSystemic lupus erythematosus (SLE) patients have a striking increase in cardiovascular (CV) comorbidity not fully explained by the Framingham risk score. Recent evidence from in vitro studies suggests that type I interferons (IFN) could promote premature CV disease (CVD) in SLE. We assessed the association of type I IFN signatures with functional and anatomical evidence of vascular damage, and with biomarkers of CV risk in a cohort of lupus patients without overt CVD.Methodology/Principal FindingsSerum type I IFN activity (induction of five IFN-inducible genes; IFIGs) from 95 SLE patient and 38 controls was quantified by real-time PCR. Flow mediated dilatation (FMD) of the brachial artery and carotid intima media thickness (CIMT) were quantified by ultrasound, and coronary calcification by computed tomography. Serum vascular biomarkers were measured by ELISA. We evaluated the effect of type I IFNs on FMD, CIMT and coronary calcification by first applying principal components analysis to combine data from five IFIGs into summary components that could be simultaneously modeled. Three components were derived explaining 97.1% of the total IFIG variation. Multivariable linear regression was utilized to investigate the association between the three components and other covariates, with the outcomes of FMD and CIMT; zero-inflated Poisson regression was used for modeling of coronary calcification. After controlling for traditional CV risk factors, enhanced serum IFN activity was significantly associated with decreased endothelial function in SLE patients and controls (p<0.05 for component 3), increased CIMT among SLE patients (p<0.01 for components 1 and 2), and severity of coronary calcification among SLE patients (p<0.001 for component 3).ConclusionsType I IFNs are independently associated with atherosclerosis development in lupus patients without history of overt CVD and after controlling for Framingham risk factors. This study further supports the hypothesis that type I IFNs promote premature vascular damage in SLE.

Tumor necrosis factor-like weak inducer of apoptosis and its potential roles in lupus nephritis

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily that functions through binding to Fn14 receptor in target cells. TWEAK has multiple biological activities. Studies show that TWEAK plays an important role in immune inflammatory diseases. Recent work has revealed that TWEAK may play an important role in the pathogenesis of kidney damage, including in systemic lupus erythematosus (SLE), where its concentration in urine was correlated with the level of activity of lupus nephritis (LN). The major focus of this review is to discuss the recent studies on TWEAK and its possible role in the pathogenesis of LN, and the therapeutic potential of modulating this pathway in LN. TWEAK plays a key role in the pathogenesis of LN through activation of multiple down-signaling pathway, inducing proinflammatory cytokines and chemokines, affecting cell proliferation/apoptosis and inducing renal IgG deposition. TWEAK blockade may be a novel therapeutic approach to reducing renal damage in SLE.

Global Trend of Survival and Damage of Systemic Lupus Erythematosus: Meta-Analysis and Meta-Regression of Observational Studies from the 1950s to 2000s

To assess systemically with meta-analysis the trend of survival and its determinants, which are hindering further improvement of survival of patients with systemic lupus erythematosus (SLE) over the past 5 decades. Retrospective, cross-sectional, and prospective observational studies addressing survival and damage in SLE patients published between 1 January 1950 and 31 July 2010 were identified in electronic databases. Using the random-effects model, effect size was calculated based on the logit of the overall 5- and 10-year survival rates. The pooled logit and its robust 95% confidence interval were transformed back into the 5- and 10-year survival rates, after adjusting for potential dependence on the data. Potential factors predicting the pooled survival rates were explored by meta-regression. Seventy-seven studies involving 18,998 SLE patients were analyzed. Between the 1950s and the 2000s, their overall survival significantly increased, from 74.8% to 94.8% and 63.2% to 91.4% for the overall 5-year and 10-year survival, respectively (P < 0.001). The survival improvement, however, appeared to slow down between 1980 and 1990. Meta-regression revealed that neuropsychiatric and renal damage negatively affected the overall 5-year survival, whereas neuropsychiatric damage remained so for the 10-year survival for the past 50 years. Furthermore, the prevalence of neuropsychiatric damage has been significantly increasing over the past 5 decades. For the past 50 years, damage involving the renal and neuropsychiatric systems has been negatively affecting survival of SLE patients. Early detection and aggressive management of renal and neuropsychiatric involvement may potentially improve further the survival of lupus patients.

Association of N‐terminal pro–brain natriuretic peptide with cardiac disease, but not with vascular disease, in systemic lupus erythematosus

Association of N‐terminal pro–brain natriuretic peptide with cardiac disease, but not with vascular disease, in systemic lupus erythematosus

Use of atorvastatin in systemic lupus erythematosus in children and adolescents

Statins reduce atherosclerosis and cardiovascular morbidity in the general population, but their efficacy and safety in children and adolescents with systemic lupus erythematosus (SLE) are unknown. This study was undertaken to determine the 3-year efficacy and safety of atorvastatin in preventing subclinical atherosclerosis progression in pediatric-onset SLE. A total of 221 participants with pediatric SLE (ages 10-21 years) from 21 North American sites were enrolled in the Atherosclerosis Prevention in Pediatric Lupus Erythematosus study, a randomized double-blind, placebo-controlled clinical trial, between August 2003 and November 2006 with 36-month followup. Participants were randomized to receive atorvastatin (n=113) or placebo (n=108) at 10 or 20 mg/day depending on weight, in addition to usual care. The primary end point was progression of mean-mean common carotid intima-media thickening (CIMT) measured by ultrasound. Secondary end points included other segment/wall-specific CIMT measures, lipid profile, high-sensitivity C-reactive protein (hsCRP) level, and SLE disease activity and damage outcomes. Progression of mean-mean common CIMT did not differ significantly between treatment groups (0.0010 mm/year for atorvastatin versus 0.0024 mm/year for placebo; P=0.24). The atorvastatin group achieved lower hsCRP (P=0.04), total cholesterol (P<0.001), and low-density lipoprotein (P<0.001) levels compared with placebo. In the placebo group, CIMT progressed significantly across all CIMT outcomes (0.0023-0.0144 mm/year; P<0.05). Serious adverse events and critical safety measures did not differ between groups. Our results indicate that routine statin use over 3 years has no significant effect on subclinical atherosclerosis progression in young SLE patients; however, further analyses may suggest subgroups that would benefit from targeted statin therapy. Atorvastatin was well tolerated without safety concerns.

The impact of obesity in systemic lupus erythematosus on disease parameters, quality of life, functional capacity and the risk of atherosclerosis

To study the effect of obesity on the quality of life (QoL), functional capacity and the risk of carotid atherosclerotic plaque formation in systemic lupus erythematosus (SLE) patients and to correlate the findings with disease parameters, activity and damage. Sixty SLE patients were clinically examined, investigated and their carotid intima media thickness (IMT) measured by ultrasonography. Assessment of the QoL, Health Assessment Questionnaire(HAQ-II), fatigue severity scale (FSS), the disease activity using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the damage by Systemic Lupus International Collaboration Clinics (SLICC)/American College of Rheumatology (ACR) damage index were performed on all patients. Patients were grouped according to their body mass index (BMI). The mean age of the patients was 28.55 8.08 years, disease duration 6.49 5.18 years with a female : male ratio of 5.67 : 1. There was a significant association of increased BMI with lupus nephritis and hypertension. In obese SLE patients, there was a significant decrease in QoL and functional capacity and obvious dyslipidemia. The IMT was increased and significantly correlated with waist circumference. In SLE patients, there is an association of BMI with dyslipidemia and decreased QoL. Its role in disease activity is not clear and obesity was associated with SLE damage accrual, especially lupus nephritis among other risk factors, including age, disease duration and increased steroid use. Increased waist circumference increases the risk of atherosclerosis.