Early detection of premature subclinical coronary atherosclerosis in systemic lupus erythematosus patients

ObjectiveTo elucidate early coronary atherosclerotic changes in premenopausal systemic lupus erythematosus (SLE) female patients without clinical cardiovascular manifestation using a 64-slice Multi-detector computed tomography (MDCT) scan to detect coronary calcification and measure coronary calcium score (CCS), and to find out its correlation to some traditional and non-traditional risk factors.MethodologySixty consecutive premenopausal SLE female patients, and sixty age and sex matched healthy subjects without known systemic, immunological, or cardiovascular disease (served as a control group) underwent clinical examination, serological analysis, and 64-slice MDCT-based coronary calcium scoring. All the clinical, serological, and MDCT parameters of the patients were correlated.ResultsCoronary calcification (CC) was seen in 21 patients (35%), the number of atherosclerotic calcified plaques ranged from 0 to 19. Calcium scores ranged from 0 to 843. In contrast to control subjects, SLE patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), total cholesterol level, low-density lipoprotein (LDL), immunoglobulin G (IgG) and IgM anti-cardiolipin antibodies, serum intracellular adhesion molecule (sICAM) and E-selectin levels. SLE patients had highly significantly more atherosclerotic plaques (3 ± 0.66 compared to 0.1 ± 0.07, p < 0.001) and higher CCS (59.2 ± 20.3 compared to 2.6 ± 1.85, p < 0.001). Significant positive correlation was found between both number of atherosclerotic plaques and CCS and total cholesterol level, LDL, cumulative prednisone dose, SLE disease activity index (SLEDAI), ESR, CRP, sICAM-1, E-Selectin, and anti-cardiolipin antibodies (p < 0.05 in all).ConclusionPre-menopausal SLE female patients free from clinical atherosclerotic vascular disease have an increased number of atherosclerotic plaques and CCS, which correlate positively with SLEDAI disease activity score, serum CRP, anticardiolipin antibodies, sICAM-1, E-Selectin, LDL level, total cholesterol level, and cumulative prednisone dose. In addition, we conclude that MDCT is a non-invasive, sensitive, reproducible, and reliable tool for accurate measurement of coronary calcification.     

Clinical significance of vitamin D deficiency and receptor gene polymorphism in systemic lupus erythematosus patients

Introduction

The vitamin D receptor (VDR) gene is a candidate for susceptibility to autoimmune disorders.

Serum leptin in systemic lupus erythematosus patients: Its correlation with disease activity and some disease parameters

Aim of the work

To evaluate serum leptin levels in systemic lupus erythematosus (SLE) patients and correlate these levels with clinical and laboratory parameters as well as disease activity using systemic lupus disease activity index (SLEDAI).

Role of syndecan-1 (CD138) in Egyptian systemic lupus erythematosus patients with lupus nephritis: Relation to disease activity

BackgroundSyndecan-1, a transmemebrane heparan-sulfate glycoprotein, is predominantly expressed by plasma cells and is readily shed and released under certain pathologic conditions and remains biologically active to plasma cells behaviour.Aim of the workTo assess the level of syndecan-1 in relation to lupus nephritis (LN) and systemic lupus erythematosus (SLE) activity.Patients and methodsThe study included 60 SLE patients subgrouped according to the presence of LN and activity. SLE disease activity index (SLEDAI) was assessed. Serum syndecan-1 level was measured.ResultsThe patients mean age was 25.9 ± 8.6 years, they were 54 females and 6 males with a disease duration of 3.8 ± 3.4 years. There was a significant difference in the level of syndecan-1 between healthy control (46.3 ± 12.2 ng/ml) and SLE patients whether they were with active LN (150.2 ± 31.1 ng/ml) (p < 0.001), extrarenal flare (86.9 ± 16.7 ng/ml) (p < 0.001) or inactive (79.1 ± 19.8 ng/ml) (p < 0.003). Syndecan-1 was significantly higher in patients with active LN compared to those with extrarenal flare and inactive disease (p < 0.001 and p < 0.001 respectively). Serum syndecan-1 level was significantly higher in patients with arthralgia, arthritis, pleurisy and pericarditis) (all p < 0.001). There was a significant correlation between syndecan-1 level and 24 h urinary proteins (r = 0.8, p < 0.0001), and inversely with the complement (C3: r = −0.54, p < 0.0001 and C4: r = −0.48, p < 0.0001). There was a significant correlation between syndecan-1 and SLEDAI (r = 0.68, p < 0.001).ConclusionSerum syndecan-1 is significantly high in active LN patients and can be a useful tool for diagnosis of active nephritis. It correlates with disease activity, consumed complement and proteinuria. It was significantly related to the presence of musculoskeletal manifestations and serositis.     

Quantitative clinical assessment of disease activity in systemic lupus erythematosus: progress report and research agenda

Summary No single test allows an adequate measure of disease activity in multisystem diseases such as systemic lupus erythematosus (SLE). In order to evaluate the spectrum of manifestations of disease activity in SLE, investigators have developed numerous ad hoc scales which have not been tested for their validity or reliability. Three instruments have been extensively studied: the British Isles Lupus Activity Group instrument (BILAG), the SLE Disease Activity Index (SLEDAI), and the Systemic Lupus Activity Measure (SLAM). All three have been demonstrated to have convergent and construct validity when compared to the clinician's judgement. The summation of the number of criteria of the American Rheumatism Association (ARA) SLE criteria has been shown to be an inadequate measure of disease activity. Standardized measures of disease activity for SLE should enhance our ability to compare results from different centers in finer distinctions than dead or alive.     

Clinical characteristics and health related quality of life (HRQoL) in Egyptian patients with systemic lupus erythematosus

Aim of the work

To study the clinical characteristics and health related quality of life (HRQoL) in systemic lupus erythematosus patients.

系统性红斑狼疮患者外周血IFN-α表达及其与疾病活动性的关系

目的研究系统性红斑狼疮(SLE)患者外周血干扰素(IFN)-αmRNA和蛋白表达水平,并分析IFN-α的表达与疾病活动性的关系,以探讨IFN-α在SLE发病中的作用。方法SYBR green dyeⅠ实时定量聚合酶链反应(PCR)方法检测外周血白细胞IFN-α的表达；酶联免疫吸附试验(ELISA)方法检测血清IFN-α的表达。结果SLE患者外周血IFNA1 mRNA的表达(2．8±3．5)显著低于对照组(12．7±10．7,P=0．000)；未用激素治疗的患者(1．9±1．8)与已经用激素治疗的SLE患者IFNA1表达量(2．8±3．5)差异无统计学意义；血清IFN-α水平明显高于正常对照组(P=0．003)；血清IFN-α水平与SLEDAI积分和抗dsDNA抗体水平呈正相关,与补体C3、C4和白细胞数量呈负相关：血清IFN-α水平与患者发热和面部红斑有关。结论SLE患者IFN-α水平与疾病活动性之间有明显的相关性,IFN-α可能在SLE发病中发挥重要作用。     

Infection in systemic lupus erythematosus patients

BackgroundInfection is a leading cause of morbidity, mortality and hospital admission in systemic lupus erythematosus (SLE) patients.Aim of the workTo study infection in SLE patients regarding site of infection, pathogenic organism, hospitalization and/or intensive care unit (ICU) admission.Patients and methodsThis study included 79 patients. SLE disease activity index (SLEDAI-2K) and damage index were evaluated. Detailed information about the site of infection and pathogens were reported.Results71 females and 8 male patients (F:M 8.9:1), with a mean age of 29 ± 9.6 years (17–55 years) and disease duration of 5.9 ± 5.7 years, 55 (69.6%) patients had infection at time of study while 24 (30.4%) did not. The SLEDAI-2 k and damage index were significantly higher in SLE patients with infection (14.2 ± 11.8 and 3.7 ± 3.7) compared to those without infection (5.9 ± 5.03 and 1.8 ± 1.3) (p = 0.03 and p = 0.045 respectively). Those with infection had a shorter disease duration (4.9 ± 5.2 vs 8.3 ± 6.2; p = 0.005), received more cyclophosphamide (56.4% vs 16.7%; p = 0.001), higher erythrocyte sedimentation rate (ESR) (75.5 ± 27.1 vs 35.8 ± 24.7 mm/1^sthr) (p < 0.0001) and consumed complement (C3) (71.1 ± 28.4 vs 97.2 ± 28.2; p < 0.0001). 17/55 (30.9%) had more than one site of infection and 46/55 (83.6%) required hospital admission. 17 (30.9%) of hospitalized patients were transferred to the ICU. The main pathogenic organisms were bacterial (40%), fungal (27.3%), viral (10.9%) and unconfirmed in 21.8%. Chest was the commonest site (40%) followed by the skin (34.4%), oropharynx (25.5%) and urinary tract (20%).ConclusionInfection is an important cause of hospital and ICU admission in SLE patients. Early disease, disease activity and damage, cyclophosphamide, ESR and consumed C3 were associated with infection in SLE.     

Auditory disorders in patients with systemic lupus erythematosus: Relation to clinical parameters

Aim of the workTo evaluate the hearing disorders in SLE patients with particular regard to their frequency and relationship to disease duration and activity.Patients and methodsTwenty female SLE patients were enrolled in the study. Assessment of disease activity was done using the SLE disease activity index (SLEDAI). Another 20 otologically healthy subjects of matched age and sex served as controls. Auditory assessment was performed and included otoscopic examination, pure tone audiometry (PTA), acoustic immittance testing and speech audiometry.ResultsThe PTA was abnormal in 13 (65%) patients; 4 had tinnitus and 1 vertigo. The PTA results showed a highly significant statistical difference from the control (p < 0.001). Otoscopic examination, acoustic immittance testing and speech audiometry of all patients were normal. A significant difference was found in the age at disease onset between those with and without abnormal PTA (p = 0.023). Moreover, there was a significantly lower hearing level (right ear) at 12,000 Hz in juvenile-onset (N = 6) (20.83 ± 3.76 db) compared to adult-onset cases (32.5 ± 15.66 db) (p = 0.02). No significant difference was present in the audiovestibular manifestations (p = 0.114), clinical, laboratory parameters or disease activity between those with or without hearing loss. However, hearing levels were significantly lower in those with lupus nephritis and those receiving hydroxychloroquine.ConclusionPure tone audiometry revealed SNHL in 65% of SLE patients. Absence of audiovestibular manifestations does not exclude inner ear affection. Age at disease onset is remarkably associated with hearing loss in SLE. Lupus nephritis and hydroxychloroquine use are associated with lower hearing levels and possible early hearing loss.     

A cross-sectional study to assess the association of systemic lupus erythematsous disease activity with levels of high sensitivity C-reactive protein

BackgroundEarlier studies have shown that active systemic lupus erythematosus (SLE), though an inflammation, is not associated with high C-reactive protein (CRP) levels. But a few recent studies have shown that high sensitivity CRP (hsCRP) may be elevated in SLE and is associated with organ damage.ObjectiveTo evaluate the association between hsCRP levels and SLE disease activity index (SLEDAI).MethodsThis cross-sectional study was conducted in 40 SLE patients. The SLEDAI was calculated and the hsCRP level was measured in the serum. Correlation between hsCRP levels and SLEDAI was assessed. Relationship of hsCRP levels with individual components of SLEDAI was also analyzed.ResultsOut of 40 patients, 38 (95%) were female. The mean age was 28.15 years. The mean SLEDAI was 27.4 ± 17.8, indicating that most of the patients had high disease activity. The mean hsCRP levels were 6.64 ± 5.09 mg/L. hsCRP levels and SLEDAI showed strong positive correlation (Pearson's correlation coefficient r = 0.91; p < 0.0001). hsCRP levels were higher in patients with serositis, nephritis, nervous system manifestations and immunological abnormalities.ConclusionhsCRP levels reflect SLE disease activity and are higher in patients with major organ involvement.     

The association between adipokines and stigmata of atherosclerosis in patients with systemic lupus erythematosus

Aim of the workEarly cardiovascular disease is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The study was designed to assess the relationship between the serum levels of adipokines and atherosclerotic risk factors in SLE patients.Patients and methods56 patients and 31 control were included. Serum levels of leptin, adiponectin, traditional and new risk factors for atherosclerosis including plasma glucose levels, lipid profile, high-sensitivity C-reactive protein (hs-CRP), vascular cell adhesion molecule-1 (VCAM-1) and homocysteine were measured. The intima-media thickness (IMT) of the carotid was measured by ultrasonography. The SLE disease activity index (SLEDAI-2k) was assessed.ResultsThe patients mean age was 30.8 ± 9.9 years, disease duration was 55.7 ± 59.3 months and were 54 (91.5%) females and 5 (8.5%) males. Serum adiponectin levels were significantly lower in patients (3.58 ± 0.4 ng/ml) compared to control (3.9 ± 0.26 ng/ml) (p < 0.001) while leptin levels were comparable. Serum adiponectin levels correlated with triglyceride (r = 0.3, p = 0.003) and high-density lipoprotein (HDL) (r = 0.2, p = 0.04). Serum leptin significantly correlated with the BMI and total cholesterol (r = 0.43, p = 0.002 and r = 0.3, p = 0.04 respectively) as well as with the anti-double stranded deoxyribonucleic acid (anti-dsDNA) (r = 0.28, p = 0.04). There was lack of a meaningful relationship between serum adiponectin and leptin levels and disease duration or risk factors such as hsCRP, VCAM, homocysteine and IMT as well as with the SLEDAI-2k or complement.ConclusionsSerum adiponectin levels inversely correlate with HDL. A significant correlation of leptin with BMI and total cholesterol was found in SLE. None of the two adipokines were associated with atherosclerosis as assessed with the carotid IMT or with the disease activity.     

European Consensus Lupus Activity Measurement is sensitive to change in disease activity in childhood‐onset systemic lupus erythematosus

Objectives To evaluate the European Consensus Lupus Activity Measurement (ECLAM) for responsiveness to change in disease activity when used in childhood‐onset systemic lupus erythematosus (cSLE). To confirm the construct validity and to characterize the measurement properties of the ECLAM by assessing its ability to predict damage and steroid requirements.

Methods

The disease courses of 66 newly diagnosed cSLE patients were reviewed. The ECLAM and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were scored for all clinic visits and hospitalizations. Damage was assessed at the end of the followup period using the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index. Disease activity at the time of diagnosis, 6 months after diagnosis, at the time of first flare, and 6 months after first flare was used to estimate responsiveness of the measures. Responsiveness was measured by the effect size, the effect size index, the standardized response mean, and the relative efficiency index (REI). The measurement properties of the ECLAM and SLEDAI over time were examined by comparing the ability of both measures to predict damage and oral steroid requirement.

Results

The ECLAM and SLEDAI are both responsive to change in disease activity irrespective of the statistic used. The ECLAM is more sensitive than the SLEDAI using the REI (all >1.9). Cumulative disease activity as measured by the SLEDAI or the ECLAM are important predictors of damage. There are no statistically important differences between the 2 measures with regard to their ability to predict steroid requirements.

Conclusions

The ECLAM has construct validity in cSLE and, like the SLEDAI, is highly sensitive to clinically important change in disease activity. The ECLAM may be more responsive. The quantitative properties of the 2 measures are very similar. The SLEDAI likely remains the preferable disease activity measure for cSLE given its overall measurement properties and ease of use.

     

Hyperprolactinemia in patients with systemic lupus erythematosus: correlation with disease activity

Aim: Recent accumulated evidence suggests that prolactin is an important immunomodulator and may have a role in the pathogenesis of systemic lupus erythematosus (SLE). Our aim was to assess the frequency of hyperprolactinemia in women with SLE and to evaluate its correlation with disease activity. Method: Plasma prolactin levels were measured in 35 women with SLE and 60 age‐ and sex‐matched healthy controls. Disease activity was assessed using the SLE disease activity index (SLEDAI). Patients with a score > 10 were considered active. In patients and controls prolactin levels were determined by immunoradiometric assay (IRMA). Results: The prolactin level was higher in SLE than in the control group: 28.5% of SLE patients versus 3.3% of controls had high prolactin levels. Patients with active disease had a trend to higher mean prolactin levels than inactive patients. SLE was active in 90% of hyperprolactinemic patients. In normoprolactinemic patients active disease was found only in 36% of patients. A statistically significant correlation was found between prolactin levels and SLE disease activity index. Conclusion: This study shows that moderate hyperprolactinemia is present in a subset of patients with SLE and that it is related to increased disease activity and major organ involvement.     

Intercellular adhesion molecules in systemic lupus erythematosus patients with lupus nephritis

Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE), and the mechanism of atherogenesis remains poorly understood. Several methods have been employed to assess endothelial function, among these is the measurement of biomarkers of endothelial activation and dysfunction [intercellular adhesion molecule (ICAM-1)]. It has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease. The objectives of this study were to determine the level of ICAM-1 as markers of endothelial dysfunction in 40 Egyptian patients who have SLE with various degrees of activity and to investigate their relationship to disease activity. Sixty people (40 with SLE and 20 healthy as the control group) were the subject of this study; their clinical disease activity was scored according to the SLE disease activity index (SLEDAI), and serum sampling was obtained for ICAM-1 level assay. Renal biopsy was carried out and examined by light microscopy by a pathologist blinded to the clinical activity. The mean level of ICAM-1 was significantly higher in SLE patients with active disease (826.05 ± 367.1 Pg/ml) compared to those with inactive disease (441.33 ± 225.19 Pg/ml) and the healthy control volunteers (111.5 ± 17.36 Pg/ml). There was a positive correlation between serum ICAM-1 and SLEDAI (r = 0.66). A high concentration of soluble ICAM-1 in SLE patients with nephritis is reported in this paper. Our finding of increased concentrations of ICAM-1 in SLE patients with nephritis underlines the importance of inflammation and endothelial involvement in this disease, but their predictive value in the disease monitoring need to be further studied.     

Thyroid dysfunction in patients with systemic lupus erythematosus (SLE): relation to disease activity

We examined the prevalence of thyroid dysfunction and the production of anti-thyroid antibodies (ATA) in patients with systemic lupus erythematosus (SLE) and assessed the association between ATA production and SLE disease activity status. Seventy-seven patients who met the American College of Rheumatology classification criteria for SLE participated in the study. Fifty-two individuals served as a control group. Demographic, clinical information and SLE disease activity (SLEDAI) status were collected from all patients. The sera of all participants were tested for free thyroxine (FT4), thyroid-stimulating hormone (TSH), anti-thyroglobulin (ATg) and anti-thyroid peroxidase (TPO). A SLEDAI score of > or =6 was considered clinically significant. The results of the thyroid function tests and ATA were compared between the study group and the control group. ATA levels were compared between the patients with a SLEDAI score of > or =6 to those with a SLEDAI score of <6. Hypothyroidism was detected in 11.6% of SLE patients compared to 1.9% in the control group. None of the patients or controls had evidence of hyperthyroidism. No statistically significant difference was observed in the levels of ATg or TPO between the study group and the control group. No correlation was found between ATA levels and the degree of the disease activity. Among the different variables tested in this study, hypothyroidism was the only significant abnormal finding in SLE patients. No association was found between the SLEDAI score and the prevalence of ATA production. Larger controlled, longitudinal studies are necessary to confirm these findings and elucidate the role played by ATA in the pathogenesis of thyroid dysfunction in SLE patients.     

系统性红斑狼疮细胞与其病情活动性的相关性研究

目的 观察系统性红斑狼疮（SLE）患者外周血狼疮细胞（LEC）形态的变化，探讨其与SLE疾病活动性的关系。方法 采用经典改良血块法观察了50例SLE疾病活动期和30例SLE非活动期患者外周血LEC形态，同时与血清自身抗体、补体及SLE疾病活动指数（SLEDAI）对比研究。结果 特殊形态的LEC与自身抗体的抗dsDNA抗体和抗核小体抗体（AnuA）（r=0．588，P=0．056；r=0．759，P=0．135），补体C3和C4（r=-0．648，P=0．058；r=-0．589，P=0．057）及SLEDAI（r=0．686．P〈0．05）具有明显相关性。SLE活动期组特殊型LEC、自身抗体和补体与SLE非活动期组差异有统计学意义（P〈0．01）。当自身抗体和补体与SLEDAI无相关性时，特殊型LEC仍具有良好的相关性（r=0．786，P〈0．05）。结论 特殊型LEC与自身抗体、补体及SLEDAI有明显的相关性，可作为判断SLE疾病活动性的独特指标。     

Utero-placental and cerebrovascular indices in pregnant women with systemic lupus erythematosus: Relation to disease activity and pregnancy outcome

Aim of the workTo assess maternal and fetal vascular indices in SLE patients during pregnancy, and the impact of disease activity on these vascular indices.Patients and methods30 pregnant SLE patients and 30 age -matched healthy females with uncomplicated pregnancies were assessed during the third trimester using ultrasonography (US) and Doppler study to detect fetal biometry, the uterine, umbilical (UA) and fetal middle cerebral (MCA) arterial resistance (RI) and pulsatility (PI) indices, as well as cerebro-placental ratio (CPR). Disease activity was determined using the SLE Disease Activity Index (SLEDAI).ResultsThe mean uterine artery PI, RI and the UA-PI in SLE group were significantly higher than controls (p value < 0.001), but no significant difference as regards UA-RI (p = 0.68) between both groups. There was unilateral uterine artery notch in 20% and bilateral in 6.7% while it was absent in 73.3%. The MCA-PI was significantly lower in SLE group (p = 0.003), Where the MCA-RI showed higher values than control (p < 0.001). The CPR showed a lower significant values for SLE group compared to controls (p < 0.001), while the PR interval was significantly higher in SLE group (p = 0.006). Fetal biometry showed no significant difference between two groups apart from higher abdominal circumference (AC) values in controls (p = 0.01). There was no significant correlation between abnormal vascular indices or biometric parameters and SLEDAI score (p > 0.05).ConclusionPregnancies in SLE are associated with abnormal maternal and fetal vascular indices. Doppler US can identify at-risk pregnancies and optimize the time of delivery; confirming a good pregnancy outcome.     

Role of glutathione S-transferases polymorphisms and monocyte CD64 expression in Egyptian patients with systemic lupus erythematosus

Aim of work

To study the genetic variants of glutathione S-transferases and monocyte CD64 expression in systemic lupus erythematosus patients and to evaluate their role in disease susceptibility, activity and damage.