Serum deoxyribonuclease I and clinical activity in systemic lupus erythematosus

Summary Serum deoxyribonuclease I (DNase I) activity in systemic lupus erythematosus (SLE) patients was shown to be lower than that of healthy laboratory personnel, rheumatoid arthritis, and scleroderma patients (P<0.001). The decrease in DNase I activity in SLE sera was not due to the effect of various autoantibodies or to heat labile DNase I inhibitor. A relationship between serum DNase I activity and active SLE was demonstrated. Patients with active lupus nephritis had the lowest levels of enzymatic activity.     

Serum resistin,insulin resistance and carotid intima-media thickness as an indication of subclinical atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo evaluate resistin level in systemic lupus erythematosus (SLE) patients and to assess the relationship with insulin resistance, disease characteristics, inflammatory markers and carotid intima-media thickness (CIMT) as a marker of subclinical atherosclerosis.Patients and methodsThirty adult SLE patients and twenty age and sex-matched control were enrolled. All patients were subjected to history taking, clinical examination and assessment of anthropometric measurements. Laboratory investigations included serum resistin, measures of insulin resistance, highly sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) and lipid profile. Carotid duplex was performed for measurement of CIMT. SLE disease activity index (SLEDAI-2k) and damage index were evaluated.ResultsThe 30 patients were 23 (76.7%) females and 7 (23.3%) males (F:M 3.3:1) with a mean age of 30.9 ± 7.9 years. The disease duration was 4.8 ± 1.8 years. The mean serum resistin in patients was 7.7 ± 2.9 ng/dl and in control was 8.5 ± 5.1 ng/dl (p = 0.8). The ESR and hs-CRP were significantly increased (p < 0.001) and the high-density lipoprotein (HDL) decreased (p < 0.001). The mean CIMT was significantly increased in cases (0.62 ± 0.16 mm) compared to control (0.51 ± 0.11 mm)(p = 0.006). Serum resistin significantly correlated with hs-CRP, HDL and anti-nuclear antibody (p = 0.027, p < 0.001,p = 0.013 respectively). There was no significant correlation between resistin and markers of insulin resistance, SLEDAI-2 k and CIMT.ConclusionResistin expression in the serum of patients with SLE was not significantly higher than controls. Although resistin was correlated with two cardiovascular risk factors (HDL-C, hs-CRP), it did not correlate significantly with insulin resistance, disease activity, damage index and CIMT in SLE patients.     

Resistin in systemic lupus erythematosus: Relation to lupus nephritis and premature atherosclerosis

BackgroundLupus nephritis (LN) is one of the most severe complications of SLE. SLE patients have a greater risk of developing premature atherosclerosis. Resistin is an adipocyte-secreted peptide. It has pro-inflammatory and atherogenic effects.Aim of the workTo assess the serum levels of resistin in SLE patients and to evaluate it as a marker of nephritis and premature atherosclerosis.Patients and methodsThis study included 50 SLE nonpregnant female adult (mean age 23.1 ± 6.9 years) patients as well as 40 healthy volunteers matched in age and sex as a control group. Serum levels of resistin were assayed using enzyme-linked immunosorbent assay (ELISA). All patients and controls underwent laboratory investigations and carotid duplex. Disease activity was assessed using SLE Disease Activity Index (SLEDAI). Renal biopsy was performed for SLE patients with LN.ResultsThere was a highly statistically significant increase in mean serum resistin levels (14.1 ± 3.88 ng/ml) in patients versus the control group (6.44 ± 1.34 ng/ml) being more obvious in those with LN. Resistin had a significant positive correlation with markers of inflammation, SLEDAI and carotid intima media thickness (CIMT).ConclusionSerum level of resistin may serve as a marker of LN and atherosclerosis in SLE patients. A more aggressive control of the underlying inflammatory process along with the control of traditional risk factors (hypertension and cholesterol) may be beneficial in reducing the risk factors of renal and atherosclerotic involvement in SLE. Therapeutic approaches with drugs that target resistin might be useful in the treatment of SLE.     

Metabolic syndrome in patients with systemic lupus erythematosus from South India

ObjectivesTo find the prevalence of metabolic syndrome in systemic lupus erythematosus (SLE) compared to controls and to identify association of metabolic syndrome with SLE disease activity and damage.MethodsA total of 82 SLE and 82 healthy controls were studied. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III), consensus definition for Asian Indian Adults and World Health Organisation (WHO) 1999 definition, and associations with lupus characteristics, disease activity, and damage were examined. Insulin resistance (IR) was estimated using the homeostasis model assessment for IR (HOMA-IR).ResultsMetabolic syndrome was present in 24.39% SLE and 12.19% controls (p < 0.04) by NCEP ATP III criteria; 29.26% SLE and 19.51% controls (p = 0.14) by consensus definition for Asian Indians; 18.2% SLE and 7.31% controls (p < 0.035) by WHO 1999 criteria.Hypertension and hypertriglyceridemia were more frequent in SLE than in controls. Mean body mass index, diastolic and systolic blood pressure, triglycerides, and total cholesterol were higher in SLE than in controls. HOMA-IR (median, range) was 1.31 (0.06–9.32) and 1.55 (0.01–7.92), p = 0.09 in SLE and controls, respectively. There was no association of metabolic syndrome with disease activity/damage and prednisolone use. SLE patients with metabolic syndrome had a significantly longer duration of disease compared to patients without metabolic syndrome.ConclusionSouth Indian SLE patients have higher prevalence of NCEP ATP III and WHO defined metabolic syndrome compared to healthy controls. SLE patients have an altered lipid profile, but there was no IR and no association of metabolic syndrome with disease activity or damage.     

Hemorheological parameters are related to subclinical atherosclerosis in systemic lupus erythematosus and rheumatoid arthritis patients

Objectives

Rheological characteristics of blood are strongly linked to atherothrombosis in the general population, but its contribution to atherosclerosis in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is currently unclear. This work examines the relationship between blood rheology, traditional cardiovascular (CV) risk factors, inflammation and subclinical atherosclerosis in SLE and RA.

Methods

Whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte deformability (ED), aggregation (EA) and erythrocyte NO production were measured in 197 patients (96 SLE and 101 RA) and compared to 97 controls, all females without previous CV events. Clinical information was obtained and fasting lipids and acute phase reactants were measured. The relationship between hemorheological parameters, CV risk factors and inflammation was assessed in patients and the impact of these variables on carotid intima-media thickness (cIMT) was evaluated in univariate followed by multivariate regression analyses.

Results

WBV and ED are significantly lower in patients, while EA is elevated as compared with controls. Hemorheological disturbances correlate with CV risk factors and markers of inflammation and are more profound in patients with metabolic syndrome. Multivariable analysis showed that menopause (OR 34.72, 95%CI 4.44–271.77), obesity (OR 4.09, 95%CI 1.00–16.68) and WBV (OR 3.98; 95%CI 1.23–12.83) are positively associated whereas current corticosteroid dose (OR 0.87; 95%CI 0.78–0.98), and erythrocyte NO production (OR 0.16; 95%CI 0.05–0.52) are negatively associated with cIMT.

Conclusion

Disturbed hemorheological parameters in SLE and RA women are related to the presence of CV risk factors and inflammation. WBV and erythrocyte NO are independently associated with the early stages of atherosclerosis.     

Serum L-ficolin levels in patients with systemic lupus erythematosus

Abstract

Objective L-ficolin plays an important role in innate immunity and is involved in apoptosis. The objective of this study was to investigate the relationship between serum L-ficolin levels and clinical manifestations in patients with systemic lupus erythematosus (SLE).

Methods Serum L-ficolin levels were determined by enzyme-linked immunosorbent assay in 66 SLE patients and 50 healthy controls.

Results Median serum L-ficolin levels were 5.0 and 8.7 μg/ml in SLE patients and controls, respectively (p = 0.0001). There were no significant differences in serum L-ficolin levels between the active disease group [SLE Disease Activity Index (SLEDAI) > 6] and the inactive disease group (SLEDAI < 5). Decreased serum L-ficolin levels were associated with thrombocytopenia (median of with vs. without thrombocytopenia 3.4 vs. 5.3 μg/ml, p = 0.008). There were no correlations between serum L-ficolin levels and SLEDAI, serum C3, or serum C4 levels.

Conclusion The association between L-ficolin and thrombocytopenia suggests a pathogenic role for L-ficolin in thrombocytopenia in SLE.     

Risk factors of vertebral fractures in women with systemic lupus erythematosus

The aim of the current study was to analyze the role of traditional and systemic lupus erythematosus (SLE)-related risk factors in the development of vertebral fractures. A cross-sectional study was performed in women with SLE attending a single center. A vertebral fracture was defined as a reduction of at least 20% of vertebral body height. Two hundred ten patients were studied, with median age of 43 years and median disease duration of 72 months. Osteopenia was present in 50.3% of patients and osteoporosis in 17.4%. At least one vertebral fracture was detected in 26.1%. Patients with vertebral fractures had a higher mean age (50 ± 14 vs. 41 ± 13.2 years, p = 0.001), disease damage (57.1% vs. 34.4%, p = 0.001), lower bone mineral density (BMD) at the total hip (0.902 ± 0.160 vs. 982 ± 0.137 g/cm², p = 0.002), and postmenopausal status (61.9% vs. 45.3%, p = 0.048). Stepwise logistic regression analysis revealed that only age (p = 0.001) and low BMD at the total hip (p = 0.007) remained as significant factors for the presence of vertebral fracture. The high prevalence of vertebral fractures in the relatively young population implies that more attention must be paid to detect and treat vertebral fractures.     

Serum metabolomic profiling in patients with systemic lupus erythematosus by GC/MS

Objectives: The aim of this study is to characterize the serum metabolic profiles of patients with systemic lupus erythematosus (SLE) using metabolomics.

Methods: Serum samples were collected from patients with SLE (n?=?80) and gender- and age-matched healthy controls (n?=?57). Metabolite profiles were performed with gas chromatography–mass spectrometry in conjunction with multivariate statistical analysis, and possible biomarker metabolites were identified.

Results: SLE and disease severity-related metabolic phenotypes were identified in sera. Parameters of the metabolomic model were correlated with SLEDAI (SLE disease activity index) scores in SLE. The metabolic signature of SLE patients comprised metabolite changes associated with amino acid turnover or protein biosynthesis, saccharometabolism, lipid metabolism, and gut microbial metabolism. Disease activity-related alterations included glutamate, 2-hydroxyisobutyrate, citrate, glycerol, linoleic acid, and propylparaben metabolites. Parts of endogenous metabolites related to SLE had the relationship with serum immunological parameters and organ manifestations. Moreover, receiver operating characteristic curve analysis revealed a higher diagnosis accuracy of endogenous metabolites.

Conclusions: Our study distinguished serum metabotypes associated with SLE and disease activities. The implementation of this metabolomic strategy may help to develop biochemical insight into the metabolic alterations in SLE.     

Maternal and fetal outcomes of 72 pregnancies in Argentine patients with systemic lupus erythematosus (SLE)

The purpose of the following study was to analyze maternal and fetal outcomes in pregnant patients with systemic lupus erythematosus (SLE) and the influence of SLE exacerbations on those pregnancies. Seventy-two pregnancies in 61 SLE patients treated between January 1986 and February 2004 in Hospital de Clínicas “José de San Martin” were reviewed retrospectively. Patient age was 28.1 ± 6.2 years (mean±standard deviation [SD]). Mean SLE duration was 4.5 ± 3.2 years (range 6 months–10 years). No patient acquired the disorder during gestation. Four (5.5%) patients had signs of active disease at the beginning of her pregnancy. Sixteen patients, accounting for 20 pregnancies, had a history of lupus nephritis. Nine patients met secondary antiphospholipid syndrome criteria and had 13 pregnancies. There were 14 exacerbations of the disease during pregnancy (19.4%), with most flares being mild. The most common obstetric complications were gestational hypertension in 15 pregnancies (20.8%) and preeclampsia in 8 pregnancies (11%). Forty-six percent of pregnancies ended in preterm deliveries. There were 62 live births (1 twin birth; 85%), 6 stillbirths (8%), and 5 spontaneous abortions (7%). Thirty-nine percent of newborns had low birth weight. Adequate pregnancy follow-up and delivery care by an interdisciplinary team in Argentine SLE patients with no pre-gestational preparation resulted in maternal and fetal outcomes similar to those seen in world reference centers.     

Serum adiponectin levels are associated with presence of carotid plaque in women with systemic lupus erythematosus

Background and aimSystemic lupus erythematosus (SLE) is associated with accelerated atherogenesis. Traditional risk factors do not seem to fully explain this process in patients with SLE and no other imaging/serum biomarkers have so far improved risk stratification. Here, we focused on the role of adiponectin in women with SLE.Methods and resultsThis is a sub-analysis of a validated cohort enrolling eighty females (age 18–65 years) affected by SLE. Patient underwent a single blood sampling and carotid echography. Serum adipocytokines (i.e. leptin, resistin and adiponectin) were assessed by enzyme-linked immunosorbent assay (ELISA).Patients with a carotid plaque (n = 23) were older, with longer duration of the disease, chronic use of corticosteroids, and immunosuppressive therapies. As expected, patients with a carotid plaque had increased vascular risk and high serum levels of inflammatory biomarkers, total and LDL cholesterol and adiponectin. Significant positive correlation between serum adiponectin and presence of a carotid plaque was found independently of patient age, SCORE Risk Charts, duration of disease, and SLE treatments.ConclusionsThese results indicate that high serum adiponectin is associated with accelerated carotid atherosclerosis in SLE young women and it might be useful to improve vascular risk stratification in this patient setting.     

Multiple avascular necrosis in a patient with systemic lupus erythematosus/systemic sclerosis overlap syndrome

A white female patient developed overlapping features of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) with severe pulmonary compromise. She was treated with steroids and azathioprine, which improved her clinical condition and spirometric status. In May 2002 she presented with continuous pain in her left ankle that continued even during rest and under treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Magnetic resonance imaging (MRI) showed multiple avascular necrosis (AVN). Rest and kinesitherapy were indicated for 1 year, and gradually an orthosis was introduced allowing the patient to walk normally.     

Prevalence and risk factors of vertebral fracture in female Japanese patients with systemic lupus erythematosus

Abstract

Objective We examined the prevalence and risk factors of vertebral fracture in female Japanese patients with systemic lupus erythematosus (SLE).

Methods We performed lateral radiographs of the thoracic and lumbar spine and bone mineral density (BMD) measurements and collected demographic, lifestyle, clinical, and treatment characteristics of 52 SLE patients. Vertebral fractures were defined as a >20 % reduction of vertebral body height. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were computed to assess the strength of associations between vertebral fractures and selected factors among SLE patients.

Results At least one vertebral fracture was detected in 50 % of SLE patients. A history of previous bone fracture was significantly associated with an increased risk of vertebral fractures among SLE patients (adjusted OR = 14.8, 95 % CI = 1.62–134; P = 0.017). Daily use of tea or coffee was marginally associated with a decreased risk of vertebral fractures among SLE patients (adjusted OR = 0.11, 95 % CI = 0.01–1.01; P = 0.051).

Conclusion The high prevalence of vertebral fracture in SLE patients (50 %) indicates that we need to assess the lateral spine radiograph in more female Japanese SLE patients regardless of BMD and use of corticosteroids, although additional studies are warranted to confirm the findings suggested in this study.     

Shrinking lung syndrome in systemic lupus erythematosus patients with dyspnea

Aim of the workTo identify the frequency of shrinking lung syndrome (SLS) in systemic lupus erythematosus (SLE) with dyspnea and study the clinical characteristics and differences in disease activity and damage.Patients and methodsThe study included 47 SLE patients complaining of dyspnea. SLS was considered in those with exertional dyspnea, restrictive pulmonary function tests (PFTs) and elevated copula of the diaphragm. Full history taking, thorough clinical examination, laboratory and relevant radiological investigations were performed for all the patients. Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics (SLICC) indices were compared. High resolution CT chest was performed for patients with radiological findings consistent with SLS.ResultsThe mean age of the patients was 29.43 ± 7.45 years, mean disease duration 5.18 ± 3.62 years. The SLS was present in 8 patients (17.02%). There was bilateral elevation of the diaphragm copulae in 25% of SLS patients and two had associated basal atelectatic bands. The serum uric acid was significantly higher in those with SLS while the 24 h urine protein was significantly lower and C4 normalized. The levels of SLEDAI and SLICC tended to be lower in those with SLS, yet there was no significant difference from those without. The demographic features, clinical and laboratory manifestations, disease activity and damage scores, PFTs and radiological findings of the SLE patients are presented.ConclusionIn SLE patients with dyspnea, SLS should be looked for as it is present in a high proportion of cases.     

Cardiometabolic and immune factors associated with increased common carotid artery intima-media thickness and cardiovascular disease in patients with systemic lupus erythematosus

Background and aimPatients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear.Methods and resultsFifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4⁺HLA-DR⁺ and CCR5⁺ T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets.ConclusionHDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which ‘classic’ CV risk factors give a continuous contribution, together with immunological factors (CD4⁺HLA-DR⁺ T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.     

Risk factors for cataracts in a cohort of Egyptian systemic lupus erythematosus patients

Aim of the workThis study was undertaken to evaluate cataract risk factors in Egyptian systemic lupus erythematosus (SLE) patients.Patients and methodsA cohort of 150 consecutive adult SLE patients was included. None of the patients was diabetic or had cataract before steroids treatment for SLE. Detailed medical and ophthalmological histories were taken. Thorough clinical examination was performed with assessment of SLE disease activity index (SLEDAI) and systemic lupus international collaborating clinics damage index (SLICC DI), along with routine blood tests. Slit lamp examination was done to assess the anterior segment of the eye especially the lens to detect the type and degree of cataract.Results150 SLE patients were studied with a mean age of 37.16 ± 11 years; 129 females and 21 males and a mean disease duration of 11 ± 5.7 years. Their mean SLEDAI was 4.1 ± 3.78 and SLICC/DI 2.1 ± 1.3. The frequency of cataract was 18% (n = 27); 22.2% of them were cortical and 77.8% were posterior subcapsular with mild-moderate degree. Glaucoma was present in only 2%. A significant increase in age, disease duration, age at onset, SLICC/DI, cumulative steroid dose and hydroxychloroquine (HCQ) dose was found in those with cataract compared to non-cataract patients (p < 0.05). The age, age at onset, disease duration, SLICC/DI and cumulative steroid dose were significant independent factors increasing the probability of cataract occurrence among SLE patients (p < 0.01).ConclusionAlthough corticosteroids are prescribed to control SLE symptoms, these results highlight potential risks associated with their use, especially cataracts, which require careful and routine ophthalmologic examination and follow up.     

系统性红斑狼疮患者并发心律失常的类型及相关危险因素分析

目的 分析系统性红斑狼疮（SLE）患者并发心律失常的类型及相关危险因素。方法 回顾性分析2003年11月至2013年2月期间经本院确诊为SLE的559例住院患者（男60例,女499例）,将其分为心律失常组和非心律失常组,收集各项检查检验指标,采用多因素分析SLE并发心律失常的独立危险因素。结果 559例SLE患者中有142例（25. 4%）并发心律失常。其中以窦性心动过速所占比例最高（56. 34%）,其次为窦性心动过缓（16.9%）,再其次为I度房室传导阻滞和室性早搏（均为6. 34%）,其余为其他心律失常（0. 7% ~3. 5%）。单因素分析显示,SLE患者合并心律失常的危险因素有合并多系统损害、其他结缔组织病、心包积液、左房扩大、高甘油三酯、高血糖、低高密度脂蛋白、低血浆白蛋白、低钙血症、高C反应蛋白、抗Sm阳性及抗RNP阳性（P〈0. 05）。多因素分析显示,独立危险因素有抗RNP阳性、左房扩大及低血浆白蛋白（P〈0. 05）。结论 SLE患者可并发各种类型心律失常,其中以窦性心动过速最为常见;独立危险因素有抗RNP阳性、左房扩大及低血浆白蛋白。     

Clinical pattern in Egyptian systemic lupus erythematosus patients with pleuropulmonary involvement

Aim of the work

To study and analyze the clinical features of Egyptian systemic lupus erythematosus (SLE) patients with pleuro-pulmonary system involvement.

Etanercept for the treatment of intractable hemophagocytic syndrome with systemic lupus erythematosus

Abstract

A 41-year-old woman presented with continuous fever, and her laboratory data suggested the recrudescence of systemic lupus erythematosus. She was treated with 60 mg/day prednisolone. With a dose reduction of prednisolone, high fever and pancytopenia were observed again. A bone marrow biopsy revealed hemophagocytosis. The effects of steroid pulse therapy, high-dose intravenous immunoglobulin, cyclosporine A, and methotrexate were insufficient. However, after four injections of etanercept (25 mg, twice a week) subcutaneously, her symptoms had completely resolved. In such cases, therapy with etanercept may be effective.     

Risks factors for low bone mineral density in pre-menopausal Mexican women with systemic lupus erythematosus

The aim of this study was to determine the prevalence and risk factors for low bone mineral density (BMD) in women with systemic lupus erythematosus (SLE). A cross-sectional study was conducted among 100 pre-menopausal patients with SLE. Patients were evaluated using a questionnaire about the following variables: age, disease duration, disease activity, chronic disease damage, cumulative corticosteroid dose, and history of fracture. Lumbar spine and hip measurements of BMD were performed by dual absorptiometry. Univariate and multivariate statistical analyses were used to assess the relationship between risk factors and BMD. The mean age was 32.8 ± 8.7 years, and the median duration of SLE was 73.2 ± 65 months. The mean cumulative corticosteroid dose was 20.0 ± 21.3 g. The mean BMD was 1.09 ± .18 g/cm² in the lumbar spine and 1.0 ± .14 g/cm² in the hip. Osteopenia was present in 40% of patients and osteoporosis in 5%. In the multiple regression analysis, low BMD in the lumbar spine was associated with chronic disease damage and low body mass index (BMI). Low BMD in the hip was associated with cumulative corticosteroid dose and low BMI. Chronic disease damage, low BMI, and cumulative corticosteroid dose are risks factors for low BMD in pre-menopausal SLE patients. Osteopenia was found in 40% of patients, while osteoporosis was found in only 5%.