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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both clinically and scientifically, the variable organ manifestations of systemic lupus erythematosus (SLE) pose a particular challenge to rheumatologists. Validated scores for disease activity (BILAG, ECLAM, SIS, SLAM, SLEDAI), damage (SLICC/ACR damage index) and health-related quality of life (MOS SF-36) have been successfully used for years. New therapies, however, need to show improvement on outcome parameters for defined organ systems--and these are mostly ill-defined. For proliferative lupus nephritis, well designed studies have been available for years. However, these use very severe outcome parameters (renal failure, death), and therefore take at least 5 years for definitive results. Of the surrogate markers which were devised, none has proven reliable for determining outcome. The combination of shorter studies for defining hopeful strategies followed by long definitive studies, appears to be the best option at present.
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PMID:[Systemic lupus erythematosus--activity and outcome]. 1650 25

Systemic lupus erythematosus (SLE) is an autoimmune connective tisssue disease. Disregulation of proinflammatory cytokines' secrection plays a pivotal role in its etiopatogenesis. Most studies concerning serum levels of those cytokines were conducted in active SLE patients. To date, there are scarce date on proinflammatory cytokines' serum concentration in inactive SLE patients. The aim of the study was to evaluate serum level of IL-1beta, IL-6, IL-18 and TNF-alpha in inactive SLE patients. The study involved 25 SLE patients aged between 24-65 years (mean age 40.6 years) and 25 age- and sex-matched healthy volunteers. The activity of the disease was assesed by SLAM scale. Serum concentrations of IL-6 and IL18 were determined by ELISA while serum levels of TNF-alpha and IL-1beta were measured using chemiluminescensce assay. In all healthy volunteers and in 23 out of 25 SLE patients, serum level of IL-1beta was undetectable (< 5 pg/ml). Serum concentrations of IL-6, IL-18 and TNF-alpha were detectable in all SLE patients. In 9 out of 27 healthy subjects level of IL-18 was under detection limit. Serum levels of IL-6, IL-18 and TNF-alpha were significanly higher (p < 0.001) in SLE patients when compared to their concentrations in subjects from control group (3.45 pg/ml vs. 2.59 pg/ml for IL-6; 344.87 pg/ml vs. 50.31 pg/ml for IL-18; 7.72 pg/ml vs. 5.21 pg/ml for TNF-alpha, respectively). The evaluation of serum levels of proinflammatory cytokines may be a sensitive marker of disease activity which may be helpful in maintaining or withdrawing chronic therapy in SLE patients.
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PMID:[Proinflammatory cytokines in inactive lupus erythematosus patients]. 1654 13

Defective invariant natural killer T-cells (iNKT cells) have been implicated in the etiology of type 1 diabetes in nonobese diabetic (NOD) mice. In a genome scan of a cross between NOD and C57BL/6 mice, the most significant locus controlling the number of iNKT cells, referred to as Nkt1, was recently mapped to distal chromosome 1. Here, using congenic mice for this chromosomal segment, we definitively demonstrate the existence of Nkt1 and show that introgression of the C57BL/6 allele onto the NOD background improves both the number of iNKT cells and their rapid production of cytokines elicited by alpha-galactosylceramide treatment, explaining at least half of the difference between the NOD and C57BL/6 strains. Using new subcongenic lines, we circumscribed the Nkt1 locus to a 8.7-cM segment, between the NR1i3 and D1Mit458 markers, that notably includes the SLAM (signaling lymphocytic activation molecule) gene cluster, recently involved in murine lupus susceptibility. However, despite a significant correction of the iNKT cell defect, the Nkt1 locus did not alter the course of spontaneous diabetes in congenic mice. Our findings indicate a complex relationship between iNKT cells and autoimmune susceptibility. Congenic lines nonetheless provide powerful models to dissect the biology of iNKT cells.
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PMID:Genetic and functional analysis of the Nkt1 locus using congenic NOD mice: improved Valpha14-NKT cell performance but failure to protect against type 1 diabetes. 1656 43

The susceptibility locus for the autoimmune disease lupus on murine chromosome 1, Sle1z/Sle1bz, and the orthologous human locus are associated with production of autoantibody to chromatin. We report that the presence of Sle1z/Sle1bz impairs B cell anergy, receptor revision, and deletion. Members of the SLAM costimulatory molecule family constitute prime candidates for Sle1bz, among which the Ly108.1 isoform of the Ly108 gene was most highly expressed in immature B cells from lupus-prone B6.Sle1z mice. The normal Ly108.2 allele, but not the lupus-associated Ly108.1 allele, was found to sensitize immature B cells to deletion and RAG reexpression. As a potential regulator of tolerance checkpoints, Ly108 may censor self-reactive B cells, hence safeguarding against autoimmunity.
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PMID:Regulation of B cell tolerance by the lupus susceptibility gene Ly108. 1677 43

Researches on quality of life have been undertaken from dozens of years. However, there are few information about quality of life among people suffering from systemic lupus erythematosus (SLE). The aim of this study was to set predictors making possible quality of life anticipation. The participants of the studied group were 42 patients with inactive illness stage (disease severity were estimated by SLAM scale). Quality of life was measured by own questionnaire. Personal resources, which are the base of anticipation, were estimated by standardized tests (AIS, LOT, GSES). The results indicated that two of examined variables became the quality of predictors: helpless/hopeless strategy and illness acceptation.
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PMID:[Quality of life predictors among patients suffering from systemic lupus erythematosus]. 1708 Jul 41

Structural and functional changes in wall and endothelial components of arterial blood vessels underlie the accelerated vascular disease progression in systemic lupus erythematosus (SLE). Using pulse contour analysis we sought to determine if subclinical vascular abnormalities could be identified in a well-characterised cohort of patients with SLE who had no increase in traditional cardiovascular risk factors. Radial artery pressure waveforms were obtained by applanation tonometry and pressure envelopes were analysed by descriptive and model-based approaches. Waveshape morphology was quantified by a novel eigenvector approach and model-based compliance indices of the large arteries (C1, capacitative arterial compliance) and small arteries (C2, reflective arterial compliance) were derived using a third-order four-element modified Windkessel model. Data were recorded from 30 patients with SLE (mean age 44 +/- 7 years and mean SLAM-R 10 +/- 4) and 19 age-matched control subjects. Significant differences in the lower frequency sinusoidal components of the pressure waveforms were evident between groups (P < 0.05). Both C1 and C2 were significantly reduced in patients with SLE: C1 mean +/- SD 13.5 +/- 4.0 ml/mmHg x 10 versus C1 17.5 +/- 4.8 ml/mmHg x 10 (P = 0.003 in patients vs. controls, respectively) and C2 5.2 +/- 3.4 ml/mmHg x 100 versus C2 9.4 +/- 2.8 ml/mmHg x 100 (P < 0.001 in patients vs. controls, respectively). In this group of SLE patients, without an excess of traditional cardiovascular risk factors and SLAM-R scores indicating mild disease, descriptive and model-based analysis of arterial waveforms identified vascular abnormalities at a preclinical stage.
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PMID:Subclinical impairment of arterial mechanics in systemic lupus erythematosus identified by arterial waveform analysis. 1735 82

Serum concentrations of three angiogenic cytokines: vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1) and placental growth factor (PIGF) and soluble vascular cell adhesion molecule 1 (sVCAM-1), were investigated in the serum of 61 patients with systemic lupus erythematosus (SLE) and 20 healthy subjects. The possible association between serum levels of these proteins and SLE activity, as well as correlation between the concentrations of cytokines were also analysed. All of these factors were detectable in all SLE patients and the healthy control group. The median concentration of VEGF was higher in active SLE (386 pg/mL) than in inactive disease (327 pg/mL) or in the control group (212 pg/mL, p<0.004). The median serum level of SDF-1 was higher in SLE patients (1,814 pg/mL) than in the control group (1,507 pg/mL, p<0.02). The median concentration of PIGF was higher (14 pg/mL) in SLE patients than in the control group (12 pg/mL, p=0.03), and particularly in active disease (17 pg/mL) as compared to the inactive phase (13 pg/mL, p=0.01). The correlations between the levels of cytokines examined and clinical features, laboratory abnormalities and the type of treatment were also analysed. We found a positive correlation between serum concentrations of PIGF and SLE activity according to SLAM score (p=0.33, p=0.13).
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PMID:Circulating proangiogenic molecules PIGF, SDF-1 and sVCAM-1 in patients with systemic lupus erythematosus. 1796 73

The evolutionary origin of genetic diversity in the SLAM/CD2 gene cluster, implicated in autoimmune lupus susceptibility in mice, was investigated by sequence analysis of exons from six members of the cluster in 48 wild mouse samples derived from the global mouse population. A total of 80 coding region SNPs were identified among the six genes analyzed, indicating that this gene cluster is highly polymorphic in natural mouse populations. Phylogenetic analyses of these allelic sequences revealed clustering of alleles derived from multiple Mus species and subspecies, indicating alleles at several SLAM/CD2 loci were present in ancestral Mus populations prior to speciation and have persisted as polymorphisms for more than 1 million years. Analyses of nonsynonymous/synonymous ratios using likelihood codon substitution models identified several segments in Cd229, Cd48 and Cd84 that were impacted by positive diversifying selective pressures. These findings support the interpretation that selection favoring the generation and retention of functional polymorphisms has played a role in the evolutionary origin of genetic polymorphisms that are predisposing to autoimmunity.
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PMID:Prevalence and evolutionary origins of autoimmune susceptibility alleles in natural mouse populations. 1809 11

B6.Sle1b mice, which contain the Sle1b gene interval derived from lupus prone NZM2410 mice on a C57BL/6 background, present with gender-biased, highly penetrant anti-nuclear antibody (ANA) production. To obtain some insight into the possible induction mechanism of autoantibodies in these mice we compared antigen-specific T dependent (TD) and T independent (TI-II) responses between B6.Sle1b and B6 mice before the development of high ANA titers. Our results show that B6.Sle1b mice mount enhanced responses to a TI-II antigen. Additionally, the memory T cell response generated by a TD antigen also increased. This enhancement correlates with the greater ability of B cells from B6.Sle1b mice to present antigen to T cells. The SLAM Associated Protein (SAP) is critical for signaling of many of the molecules encoded by the SLAM/CD2 gene cluster, candidates for mediating the Sle1b phenotype; therefore, we also investigated the effect of sap deletion in these strains on the TD and TI-II responses as well as on ANA production. The results of these studies of responses to non-self-antigens provide further insight into the mechanism by which responses to self-antigens might be initiated in the context of specific genetic alterations.
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PMID:Antigen-specific responses and ANA production in B6.Sle1b mice: a role for SAP. 1884 19

The utility of flow mediated dilation (FMD) a measure of endothelial function is limited by operator dependence. Pulse amplitude tonometry (PAT) is a novel, less operator-dependent technique to assess endothelial function. This study compares PAT to FMD in SLE and controls. Thirty women with SLE and 31 controls were enrolled. Medications, cardiovascular disease and risk factors, SLE activity (SLAM-R) and damage (SLICC-DI) were recorded. FMD and PAT were performed simultaneously. Endothelium-independent function was assessed with nitroglycerin. Average age was 48.3 +/- 10.1 years, SLE duration 16.2 years, SLAM-R 8.3 and SLICC-DI 1.0. Framingham Risk Scores were < or =2% in most subjects. There were no differences between SLE cases and controls in FMD, PAT or response to nitroglycerin. This study found no association between FMD and PAT in SLE or controls. In the 17 SLE cases with a history of Raynaud's, correlation between FMD and PAT was 0.50 (P = 0.04). There was no difference in endothelial function assessed by FMD or PAT in SLE cases versus controls. FMD did not correlate with PAT except in SLE cases with a history of Raynaud's. Correlation between FMD and PAT may be stronger in populations with greater variation in endothelial function and more cardiovascular risk factors.
Lupus 2009 Mar
PMID:A controlled comparison of brachial artery flow mediated dilation (FMD) and digital pulse amplitude tonometry (PAT) in the assessment of endothelial function in systemic lupus erythematosus. 1921 62


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