Expression Of Systemic Lupus Erythematosus Research Articles

RETRACTION: Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus.

Y. Sheng, J. Zhang, K. Li, H. Wang, W. Wang, L. Wen, J. Gao, X. Tang, H. Tang, H. Huang, M. Cai, T. Yuan, L. Liu, X. Zheng, Z. Zhu and Y. Cui, "Bach2 Overexpression Represses Th9 Cell Differentiation by Suppressing IRF4 Expression in Systemic Lupus Erythematosus," FEBS Open Bio 11, no. 2 (2021): 395-403, https://doi.org/10.1002/2211-5463.13050. The above article, published online on 28 November 2020 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Miguel A. De la Rosa; FEBS Press; and John Wiley and Sons Ltd. The retraction has been agreed following diagnostic errors identified by the authors in the patient samples used in this study. Based on the issues identified, the editors and authors consider the conclusions substantially compromised.

Vanin-2 is expressed in peripheral blood T cells and upregulated in patients with systemic lupus erythematosus.

Members of the vanin gene family include VNN1, VNN2, and VNN3 in humans. Although the functions of vanins have been widely examined in myeloid cells, their expression and functions have not been clarified in T lymphocytes. This study aimed to elucidate the significance of Vanin-2 (VNN2) on human peripheral blood T lymphocytes and study its expression in systemic lupus erythematosus (SLE). The differential expression of Vanins was analyzed by bioinformatics. VNN2 expressions in peripheral blood T-cell subsets were analyzed by single-cell RNA sequencing data and flow cytometry. Changes of VNN2 expression before and after T-cell activation were further clarified by western blot. The function of VNN2+ cells was studied by granzyme B (GZMB) and perforin detection. Changes in VNN2+ proportions in T-cell subsets of patients with SLE were further analyzed. In the present study, only VNN2 among vanins showed distinguishable expression in T cells. VNN2+ percentages were higher in CD8+ T cells those in CD4+ T cells. VNN2+ T cells were with a higher memory T-cell composition. VNN2 expression was significantly increased after T-cell stimulation. VNN2+ T cells had higher levels of GZMB and perforin secretion than VNN2- T cells. Clinically, VNN2+ percentages in T cells of patients with SLE were upregulated. Together, these data suggested that VNN2 is expressed in peripheral blood T cells characterized more GZMB and perforin secretion, and increased VNN2+ T cells in patients with SLE could reflect altered T-cell functions in vivo.

α-Ketoglutarate-Dependent KDM6 Histone Demethylases and Interferon-Stimulated Gene Expression in Lupus.

We aimed to investigate the hypothesis that interferon (IFN)-stimulated gene (ISG) expression in systemic lupus erythematosus (SLE) monocytes is linked to changes in metabolic reprogramming and epigenetic regulation of ISG expression. Monocytes from healthy volunteers and patients with SLE at baseline or following IFNα treatment were analyzed by extracellular flux analysis, proteomics, metabolomics, chromatin immunoprecipitation, and gene expression. The histone demethylases KDM6A/B were inhibited using glycogen synthase kinase J4 (GSK-J4). GSK-J4 was tested in pristane and resiquimod (R848) models of IFN-driven SLE. SLE monocytes had enhanced rates of glycolysis and oxidative phosphorylation compared to healthy control monocytes, as well as increased levels of isocitrate dehydrogenase and its product,α-ketoglutarate (α-KG). Because α-KG is a required cofactor for histone demethylases KDM6A and KDM6B, we hypothesized that IFNα may be driving "trained immune" responses through altering histone methylation. IFNα priming (day 1) resulted in a sustained increase in the expression of ISGs in primed cells (day 5) and enhanced expression on restimulation with IFNα. Importantly, decreased H3K27 trimethylation was observed at the promoters of ISGs following IFNα priming. Finally, GSK-J4 (KDM6A/B inhibitor) resulted in decreased ISG expression in SLE patient monocytes, as well as reduced autoantibody production, ISG expression, and kidney pathology in R848-treated BALB/c mice. Our study suggests long-term IFNα exposure alters the epigenetic regulation of ISG expression in SLE monocytes via changes in immunometabolism, a mechanism reflecting trained immunity to type I IFN. Importantly, it opens the possibility that targeting histone-modifying enzymes, such as KDM6A/B, may reduce IFN responses in SLE.

Status of TWEAK DNA methylation and mRNA expression in systemic lupus erythematosus.

Draw upon research into the serum concentration, mRNA expression, and DNA methylation of TNF-like weak inducer of apoptosis (TWEAK) in the peripheral blood of systemic lupus erythematosus patients and healthy controls in an attempt to investigate the epigenetics associated with TWEAK in the pathogenesis of systemic lupus erythematosus (SLE). A total of 178 SLE patients (SLE group) and 131 sex-age matched healthy controls (HC group) were recruited. Enzyme-linked immunosorbent assays (ELISA) was used to detect serum protein concentration of TWEAK. TWEAK mRNA expression was analyzed by Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Methylation levels of the promotor of TWEAK were measured using quantitative DNA methylation analysis on the MassARRAY spectrometry. Serum TWEAK concentrations were not statistically significant in SLE patients and HCs. Nevertheless, serum TWEAK concentrations were significantly lower in patients with renal involvement when compared to those without it. Serum TWEAK concentrations were reduced in clinically active patients (SLEDAI ≥ 10) compared with clinically stable patients (SLEDAI < 10). It was also significantly associated with SLEDAI. Compared with the HC group, the TWEAK mRNA expression in the SLE group was significantly lower. The global DNA methylation levels of TWEAK in the SLE group were observed to be significantly higher than the HC group. SLE patients with renal involvement, and the clinically active patients had higher TWEAK global methylation as well as exhibited variation in certain CpG island methylation. Furthermore, TWEAK methylation negatively correlated with TWEAK mRNA expression. This study suggests that TWEAK DNA methylation is a valuable as a focus for epigenetic studies because of it potentially influencing TWEAK gene expression in SLE patients. Aberrant DNA methylation of TWEAK may be involved in the initiation and development of SLE.

Desquamative Inflammatory Vaginitis as an Expression of Systemic Lupus Erythematosus.

Desquamative Inflammatory Vaginitis as an Expression of Systemic Lupus Erythematosus.

Differential distribution of vitamin D receptor (VDR) gene variants and its expression in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder that displays an important genetic background. Vitamin D3 (VD3 ) through its receptor (VDR) plays an important immunomodulatory role in autoimmune misbalance, being capable of modulating immune responses. Genetic alterations in VDR gene may contribute to an altered risk in SLE development and clinical manifestations. We investigated VDR SNPs (single nucleotide polymorphisms) frequencies in 128 SLE patients and 138 healthy controls (HC) and mRNA differential expression in 29 patients and 17 HC regarding SLE susceptibility as well as clinical features. We observed that rs11168268 G allele (OR=1.55, p=.01) and G/G genotype (OR=2.69, p=.008) were associated with increased SLE susceptibility. The rs2248098 G allele and A/G and G/G genotypes were associated to lower SLE susceptibility (OR=0.66, p=.01; OR=0.46, p=.01; OR=0.44, p=.02, respectively). Regarding clinical features, we observed lower risk for: rs11168268 A/G genotype and nephritis (OR=0.31, p=.01); rs4760648 T/T genotype and photosensitivity (OR=0.24, p=.02); rs1540339 T/T genotype and antibody anti-dsDNA (OR=0.19, p=.015); rs3890733 T/T genotype and serositis (OR=0.10, p=.01). We identified a significant downregulation in VDR expression levels when compared patients and controls overall (p=1.04e-7 ), in Cdx-2 A/G and G/G (p=.008 and p=.014, respectively) and in patients with nephritis (p=.016) Our results suggested that VDR SNPs influence upon SLE susceptibility and in particular clinical features, acting on mRNA expression in SLE patients overall and the ones with nephritis.

P234 The effect of calcitriol on the expression of interferon signature genes in dendritic cells and macrophages in systemic lupus erythematosus

Abstract Background/Aims A number of studies have demonstrated the inverse association between vitamin D and (i) disease activity and (ii) interferon (IFN) signature gene expression in systemic lupus erythematosus (SLE). The aim of the study was to establish the effect of calcitriol supplementation to cultured macrophages and dendritic cells (DC) from a SLE patient and control, on the expression of 12 IFN signature genes, interferon regulatory factor (IRF)7 and IRF8. Methods Blood samples were collected from a 41-year-old female SLE patient who fulfilled the SLICC classification criteria for SLE and from a 36-year-old healthy female control after obtaining informed consent. Both patients had a serum 25-hydroxyvitamin D level of 25ng/ml. Peripheral blood mononuclear cells (PBMC) were isolated by using histopaque®-1077. CD83 and CD14 expression was measured by flow cytometry and cell count and viability were assessed. The PBMC suspension was cultured in 6-well plates using: (i) ImmunoCultTM DC culture kit (following kit protocol) for DC differentiation, (ii) culture medium for macrophage differentiation containing RPMI 1640 Medium, DMEM, fetal bovine serum and LPS. Following 7 days of incubation, differentiation of cells was confirmed using microscopy and flow cytometry to measure CD83 and CD14 expression. Calcitriol at a concentration of 20nM was added to half of the wells of each sample category. Following 24 and 48 hours, RNA extraction was carried out on treated and untreated samples. QuantiGene Plex technology was used to measure the expression of 12 IFN signature genes, IRF7, IRF8 and four housekeeping genes in the extracted RNA. The normalised median florescence intensity for the 12 IFN signature genes was used to calculate the IFN score. Results A significantly lower IFN score was noted at 24 hours in SLE patient dendritic cell and macrophage cell cultures and in control macrophage cell cultures treated with calcitriol when compared with respective untreated samples (p = 0.014, p = 0.034, p = 0.031 respectively). On comparing IRF8 expression in treated and untreated cell cultures, a significantly lower IRF8 expression was noted in treated macrophage cell cultures obtained from both SLE patient and control (p = 0.034, p = 0.041). No difference in IRF7 expression was noted in treated and untreated cultures for all samples. Conclusion The suppression of the interferon signature genes in dendritic cell and macrophage cell cultures with vitamin D was confirmed in the in vitro experiment carried out. In this experiment a decrease in the expression of IRF8 (known to have a VDR binding site) was also observed in macrophage cultures from both SLE patient and control. Disclosure R. Magro: None. E. Seria: None. G. Grech: None. A.A. Borg: None. C. Scerri: None.

Glomerular endothelial expression of type I IFN-stimulated gene, DExD/H-Box helicase 60 via toll-like receptor 3 signaling: possible involvement in the pathogenesis of lupus nephritis

Background Sustained type I interferon (IFN) activation via Toll-like receptor (TLR) 3, 7 and 9 signaling has been reported to play a pivotal role in the development of lupus nephritis (LN). Although type I IFN activation has been shown to induce interferon-stimulated genes (ISGs) expression in systemic lupus erythematosus, the implication of ISGs expression in intrinsic glomerular cells remains largely unknown. Methods We treated cultured human glomerular endothelial cells (GECs) with polyinosinic-polycytidylic acid (poly IC), R848, and CpG (TLR3, TLR7, and TLR9 agonists, respectively) and analyzed the expression of DExD/H-Box Helicase 60 (DDX60), a representative ISG, using quantitative reverse transcription-polymerase chain reaction and western blotting. Additionally, RNA interference against IFN-β or DDX60 was performed. Furthermore, cleavage of caspase 9 and poly (ADP-ribose) polymerase (PARP), markers of cells undergoing apoptosis, was examined using western blotting. We conducted an immunofluorescence study to examine endothelial DDX60 expression in biopsy specimens from patients with LN. Results We observed that endothelial expression of DDX60 was induced by poly IC but not by R848 or CpG, and RNA interference against IFN-β inhibited poly IC-induced DDX60 expression. DDX60 knockdown induced cleavage of caspase 9 and PARP. Intense endothelial DDX60 expression was observed in biopsy specimens from patients with diffuse proliferative LN. Conclusion Glomerular endothelial DDX60 expression may prevent apoptosis, which is involved in the pathogenesis of LN. Modulating the upregulation of the regional innate immune system via TLR3 signaling may be a promising treatment target for LN.

Evaluation of serum microRNA-30e-5p expression in systemic lupus erythematosus and its association with clinical manifestations: A cross-sectional study

BackgroundMicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally. Accumulating evidence indicates that the miR-30 family takes part in the development of multiple tissues and organs, and is a potential contributor to various diseases, including autoimmune disorders such as systemic lupus erythematosus (SLE). The aim of this study was to evaluate the expression of miR-30e-5p, a member of the miR-30 family, and investigate its potential relationship to clinical characteristics and possible disease activity in an Egyptian SLE cohort. MethodsSerum samples from 40 SLE patients and 37 age and gender matched healthy subjects were tested for miR-30e-5p expression level using the Taqman quantitative reverse transcription-polymerase chain reaction. Analysis was performed using the 2−ΔΔCT method. ResultsThe mean age of the patients was 28.7±7.9 years, with a mean disease duration of 6.4±5.3 years. The median fold change in serum miR-30e-5p among our SLE cohort was significantly higher 1.748 (0.223–20.485) compared to the control group 0.877 (0.058–3.522) (P=0.02). Receiver operating characteristic curve analysis revealed that miR-30e-5p expression level can discriminate SLE patients from controls at a cut-off value ≥1.06 with the area under the curve (AUC)=0.676 (95% CI: 0.559–0.794, P=0.02), with 64.3% sensitivity and 61.5% specificity. There was no correlation between any of the demographic features, clinical manifestations (apart from serositis, P=0.013) or disease activity and miR-30e-5p levels. ConclusionOur study demonstrated elevated miR-30e-5p expression levels in serum samples of SLE patients. Apart from serositis, it was not associated with any other disease characteristics.

HIF-1α and miR-210 differential and lineage-specific expression in systemic lupus erythematosus

Systemic lupus erythematosus (SLE, lupus) is a chronic autoimmune disease characterized by loss of peripheral tolerance to nuclear self-antigens. It is increasingly recognized that aberrant T cell metabolism is a critical mediator of SLE immunopathology. Hypoxia inducible factor 1⍺ (HIF-1α) is a key transcription factor that regulates T cell metabolism in response to immune stimuli. T cell activation induces HIF-1α expression and transcriptional activation of HIF-responsive genes. HypoxamiRs are a group of microRNAs sensitive to HIF-1α transcriptional regulation that function to fine-tune the HIF-driven transcriptional program. The ‘master’ hypoxamiR, miR-210 is transcriptionally regulated by HIF-1α and negatively regulates HIF-1α activity. Although a key role for HIF-1α in has been described in a number of autoimmune and inflammatory diseases and abnormal microRNA expression profiles correlate with poor clinical outcome in a number of rheumatologic diseases, the expression and function of HIF-1α and miR-210 in lupus remains largely uncharacterized. Here we report HIF-1α and miR-210 differential and lineage-specific expression in systemic lupus erythematosus. We show that HIF-1α mRNA and protein is overexpressed in human lupus CD4+ cells but not in CD8+ or CD19+ cells. RORγt, was upregulated in human lupus lymphocytes while FoxP3 expression remained unchanged. We show that miR-210 expression in lupus-prone mice correlates with disease activity and is robustly and selectively upregulated in CD4+ cells from both human lupus patients and lupus-prone mice. Our results suggest that abnormal HIF-1α and miR-210 expression contributes to SLE immune pathology and that HIF-1α/miR-210 may represent a novel and important regulatory axis in SLE.

Evaluation of serum microRNA-30e-5p expression in systemic lupus erythematosus and its association with clinical manifestations: A cross-sectional study

BackgroundMicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally. Accumulating evidence indicates that the miR-30 family takes part in the development of multiple tissues and organs, and is a potential contributor to various diseases, including autoimmune disorders such as systemic lupus erythematosus (SLE). The aim of this study was to evaluate the expression of miR-30e-5p, a member of the miR-30 family, and investigate its potential relationship to clinical characteristics and possible disease activity in an Egyptian SLE cohort. MethodsSerum samples from 40 SLE patients and 37 age and gender matched healthy subjects were tested for miR-30e-5p expression level using the Taqman quantitative reverse transcription-polymerase chain reaction. Analysis was performed using the 2−ΔΔCT method. ResultsThe mean age of the patients was 28.7±7.9 years, with a mean disease duration of 6.4±5.3 years. The median fold change in serum miR-30e-5p among our SLE cohort was significantly higher 1.748 (0.223–20.485) compared to the control group 0.877 (0.058–3.522) (P=0.02). Receiver operating characteristic curve analysis revealed that miR-30e-5p expression level can discriminate SLE patients from controls at a cut-off value ≥1.06 with the area under the curve (AUC)=0.676 (95% CI: 0.559–0.794, P=0.02), with 64.3% sensitivity and 61.5% specificity. There was no correlation between any of the demographic features, clinical manifestations (apart from serositis, P=0.013) or disease activity and miR-30e-5p levels. ConclusionOur study demonstrated elevated miR-30e-5p expression levels in serum samples of SLE patients. Apart from serositis, it was not associated with any other disease characteristics.

Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by abnormal activation of T cells and caused by an imbalance in the production and clearance of apoptotic cells. We previously showed that the transcription regulator Bach2 regulated abnormal B-cell activation in SLE. Here, we investigated whether Bach2 was also involved in Th9 cell differentiation in SLE. We found that the proportion of Th9 cells was enhanced in the peripheral blood mononuclear cells (PBMC) of SLE patients. The PBMC and CD4+ T cells of SLE patients exhibited a decrease of Bach2 expression and an increase of IL-9 expression. Furthermore, Bach2 overexpression significantly repressed the levels of PU.1, IRF4, IL-9, and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. In addition, Bach2 overexpression inhibited the levels of IL-9 and Th9 cells, whereas IRF4 upregulation enhanced the levels of IRF4 and IL-9 and Th9 cells in the CD4+ T cells of SLE patients and healthy volunteers. The effect of IRF4 up-regulation was abolished by Bach2 overexpression. In summary, our work suggests that Bach2 overexpression represses Th9 cell differentiation by suppressing IRF4 expression in SLE, and thus, Bach2 may be a novel potential target for SLE treatment.

Abnormal membrane-bound and soluble programmed death ligand 2 (PD-L2) expression in systemic lupus erythematosus is associated with disease activity

Programmed death ligand (PD-L) 2 and PD-L1 are the second and first ligands, respectively, for programmed cell death-1 protein (PD-1), which is one of the key factors responsible for inhibitory T cell signaling, mediating mechanisms of tolerance and providing immune homeostasis. Studies have shown that PD-1 and its ligand PD-L1 are abnormally expressed in autoimmune diseases, such as rheumatoid arthritis and autoimmune hepatitis, but its other ligand, PD-L2, has rarely been studied. This study analyzed the changes in membrane-bound PD-L2 expression in peripheral blood mononuclear cells and soluble PD-L2 (sPD-L2) levels in the serum of patients with systemic lupus erythematosus (SLE) to explore the relationship between PD-L2 expression with disease activity and related test parameters. Our results showed that membrane-bound PD-L2 expression on monocytes was significantly higher and the sPD-L2 levels were significantly lower in SLE patients than in healthy subjects. Patients with active SLE accompanied by lupus nephritis, joint pain, and clinical manifestations of oral ulcers had relatively low secretion of sPD-L2. In addition, this secretion level was significantly and positively correlated with complement components 3 and 4 (C3/C4). These results suggest that PD-L2 may be a promising biomarker associated with the pathogenesis of SLE.

EP36 Vitamin D and interferon signature gene expression in systemic lupus erythematosus: a cross-sectional cohort study

Abstract Background Vitamin D deficiency is more prevalent in patients with systemic lupus eythematosus (SLE) as a result of sun avoidance. The potential negative impact of vitamin D deficiency on the disease activity of SLE has been shown in a number of studies. The expression of the interferon signature genes in SLE correlates positively with disease activity, and these genes are thought to mediate the clinical manifestations of the disease. The aim of this study was to establish whether a relationship exists between serum 25-hydroxyvitamin D level and the interferon signature gene expression in whole blood of SLE patients. Methods Informed consent was obtained from 92 SLE patients who were over the age of 18 and who fulfilled the SLICC classification criteria for SLE. The patients were interviewed and blood tests including full blood count, renal profile, calcium, 25-hydroxyvitamin D, complement 3 (C3), complement 4 (C4) and anti-double standed DNA (anti-dsDNA) titre were carried out. SLE disease activity was measured by SLE disease activity index-2K (SLEDAI-2K). RNA extraction was performed from whole blood. QuantiGene Plex technology was used to measure the expression of 12 interferon signature genes in the extracted RNA. The study was approved by the University Research Ethics Committee. Results 92.4% of the cohort studied were female. 58.7% were receiving vitamin D3 supplementation at a mean dose of 1031IU daily. 27.2% had vitamin D insufficiency (25-hydroxyvitamin D 21-29ng/ml) and 15.2% were vitamin D deficient (25-hydroxyvitamin D &amp;lt; 20ng/ml). Mean serum 25-hydroxyvitamin D was 30.75ng/ml (standard deviation 9.53 ng/ml). Median SLEDAI-2K was 4 (range 0-12). Serum 25-hydroxyvitamin D had a significant negative correlation with body mass index (BMI) (R=-0.258, p = 0.006) but there was no significant negative correlation with SLEDAI-2K or with the expression of the interferon signature genes. The expression of most interferon signatures genes measured (IFI35, OAS1, MX1, IFITM1, STAT2, IFIT3, IFIT1, STAT1, SOCS1) had a significant positive correlation with SLEDAI-2K. Conclusion This study did not show a significant relationship between serum vitamin D level and disease activity. In keeping with this, there was no significant negative correlation between serum 25-hydroxyvitamin D and interferon signature gene expression. Further prospective studies and randomised controlled trials are required to study this relationship in greater depth. Disclosures R. Magro None. C. Saliba None. L. Camilleri None. C. Scerri None. A.A. Borg None.

Rare variants in non-coding regulatory regions of the genome that affect gene expression in systemic lupus erythematosus

Personalized medicine approaches are increasingly sought for diseases with a heritable component. Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease resulting from loss of immunologic tolerance, but the genetic basis of SLE remains incompletely understood. Genome wide association studies (GWAS) identify regions associated with disease, based on common single nucleotide polymorphisms (SNPs) within them, but these SNPs may simply be markers in linkage disequilibrium with other, causative mutations. Here we use an hierarchical screening approach for prediction and testing of true functional variants within regions identified in GWAS; this involved bioinformatic identification of putative regulatory elements within close proximity to SLE SNPs, screening those regions for potentially causative mutations by high resolution melt analysis, and functional validation using reporter assays. Using this approach, we screened 15 SLE associated loci in 143 SLE patients, identifying 7 new variants including 5 SNPs and 2 insertions. Reporter assays revealed that the 5 SNPs were functional, altering enhancer activity. One novel variant was linked to the relatively well characterized rs9888739 SNP at the ITGAM locus, and may explain some of the SLE heritability at this site. Our study demonstrates that non-coding regulatory elements can contain private sequence variants affecting gene expression, which may explain part of the heritability of SLE.

Association between TL1A gene polymorphisms and systemic lupus erythematosus in a Chinese Han population.

Our previous studies showed elevated tumor necrosis factor-like ligand 1 aberrance (TL1A) expression in systemic lupus erythematosus (SLE). However, TL1A polymorphisms with SLE susceptibility remain to be elucidated. In addition, we made meta-analysis to evaluate the relationship of TL1A polymorphisms and autoimmune diseases owing to inconsistent results. The present research was carried out by 404 SLE, 150 primary Sjogren's syndrome (pSS) patients, and 574 healthy individuals. Three TL1A polymorphisms (rs3810936, rs6478109, rs7848647) were genotyped using TaqMan genotyping assay. Then, the meta-analysis was performed by collecting the present case-control study and previously published research. Results showed that genotypes of rs3810936, rs7848647 were different between SLE patients and healthy controls, whereas no significant association was observed in the three polymorphisms and pSS patients. Genotypes distribution of rs6478109, rs7848647 were strongly related to lupus nephritis within SLE (p = 0.004, p = 0.011), respectively. Moreover, combined meta-analysis consisted of ten comparative research involving 4,305 patients and 5,600 controls. An association between autoimmune diseases and rs6478109 polymorphism was found. Our findings indicate that gene polymorphisms (rs3810936, rs7848647) of TL1A might correlate with lupus.

Comparative Analysis of VEGF expression in Systemic Lupus Erythematosus with and without nephritis

T his work aims at evaluating the level of Vascular Endothelial Growth Factor (VEGF) in systemic lupus erythematosus (SLE) patients and studying its association with diseasing the activity and lupus nephritis(LN). The study was carried out on 40 SLE, 40 LN patients and 20 matched controls. Plasma levels of (VEGF) expression were measured using ELISA technique. Forty SLE and 40 LN patients with a mean age of (31.62±8.27) years while 20 healthy controls were (30.28±9.02) years and the SLE Disease Activity Index (SLEDAI) was (9.1±5.5). In the SLE patients, anti-nuclear antibodies (ANA) was positive in 47.5% and the anti-double stranded deoxyribonucleic acid (Anti-ds DNA) was positive in 52.5% of the patients while in LN (ANA) was positive in 47.5% of patients. Anti-ds DNA was positive in 62.5%. VEGA expression level was significantly increased in LN with mean (470.1±369.4U/ml) compared to the SLE patients with mean (183.54±95.03) with a p value (P=0.0001). A comparative analysis between immunological and biochemical data of the SLE patients and the lupus nephritis patients show an increase in the mean levels of ESR and creatinine in lupus nephritis patients compared to the SLE patients (P<0.005). VEGF level in the SLE patients is not associated with skin ulcer, Oral ulcers, malar rash, arthritis, proteinuria and anemia (P<0.05) while in the LN patients, it statistically significant increased with skin ulcer, Oral ulcers, malar rash, arthritis and anemia (P<0.05). It could be concluded that VEGF level is higher in the lupus nephritis group compared to the SLE without nephritis and control groups.

Exercise Increases Insulin Sensitivity and Skeletal Muscle AMPK Expression in Systemic Lupus Erythematosus: A Randomized Controlled Trial.

www.ClinicalTrials.gov, identifier NCT01515163.

CD26 mRNA expression in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease which involves several organs.CD26 is a multifunctional molecule that has an extracellular domain with dipeptidyl peptidase IV activity which digests crucial inflammatory molecules. CD26 plays an important role in T-cell activation and enhances immune responses. This study was carried out to evaluate the level of CD26 gene expression in SLE patients. Forty-six SLE patients and 44 healthy controls voluntarily participated in this study. Based on the SLE disease activity index (SLEDAI), the patients were divided into two subgroups, those with active disease (n=24) and those with inactive disease (n=22). Patients were also subgrouped according to renal involvement, as those with lupus nephritis (n=17) and those without lupus nephritis (n=29). Their CD26 mRNA levels in peripheral blood cells were analyzed by quantitative RT-PCR. CD26 mRNA expression increased 3.6-fold in SLE patients in comparison with the controls (p 0.05). Although CD26 mRNA expression in patients with lupus nephritis was 2.76-fold higher than those without nephritis, the difference was not statistically significant (p>0.05). CD26 gene expression in peripheral blood cells of SLE patients significantly increased over that of the controls. This increase was not affected by the disease activity nor did it show any significant correlation with complications in organs.

The effect of vitamin D on disease activity, fatigue and interferon signature gene expression in systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is multi-system autoimmune disorder, whose pathogenesis involves several cascades that lead to the production of interferon alpha, which then mediates the manifestations of the disease. In SLE, the overexpression of interferon regulated genes, produce a unique interferon signature. This has a positive correlation with disease activity. Vitamin D deficiency is highly prevalent in SLE; the role of vitamin D in the course and prognosis of SLE is unknown. Vitamin D deficiency has been associated with a higher disease activity in SLE. Fatigue is also highly prevalent in SLE; its aetiology is multi-factorial. There is limited evidence on the relationship between vitamin D, fatigue and interferon signature gene expression. Further studies on this will establish whether treatment of vitamin D deficiency in SLE, has any significant effect on the level of fatigue and disease activity, and whether this could be due to the suppression of interferon signature gene expression.