Etiology Of Systemic Lupus Erythematosus Research Articles

The potential causal association between systemic lupus erythematosus and endocrine and metabolic disorders in the East Asian population: A bidirectional two-sample Mendelian randomization study.

Observational studies indicate a significant correlation between systemic lupus erythematosus (SLE) and endocrine and metabolic disorders, but the causal association between SLE and endocrine and metabolic disorders remains unclear due to the reverse causality and confounding biases commonly presented in conventional observational research. This study endeavors to uncover the causal association between SLE and three common endocrine and metabolic disorders, including Graves' disease (GD), type 2 diabetes mellitus (T2DM), and osteoporosis (OP). We used genome-wide association study data for SLE and three endocrine and metabolic disorders in an East Asian population, employing bidirectional two-sample Mendelian randomization (MR) analysis and sensitivity analysis to ascertain the causal association between SLE and endocrine and metabolic disorders. A multiplicative random-effect inverse-variance weighted approach revealed a significant positive correlation between SLE and an elevated risk of GD with an odds ratio (OR) of 1.12 (95% CI: 1.04-1.22, p < .01), and inverse-variance weighted (IVW) analysis also indicated that SLE increased the risk of OP with an OR of 1.035 (95% CI: 1.003-1.068, p < .05). Additionally, GD causally affected SLE in an IVW analysis after Bonferroni correction, with an OR of 1.33 (95% CI: 1.19-1.49, p < .05/3), but the application of multivariable MR analysis resulted in the absence of a causal association of GD on SLE (OR 1.047, 95% CI: 0.952-1.151, p > .05). Lastly, the robustness and validity of the findings were verified through a sensitivity analysis. We confirmed that SLE has a causal effect on GD as well as OP, but no evidence exists to substantiate a causal link between SLE and T2DM. Our study offers valuable contributions for uncovering the etiology of SLE and endocrine and metabolic disorders and furthering disease risk research while providing potential targets for disease monitoring and therapeutic intervention.

Qualitative Proteome-wide Lysine Crotonylation Profiling Reveals Protein Modification Alteration in the Leukocyte Extravasation Pathway in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a severe systemic autoimmune disease with multiple manifestations. Lysine crotonylation (Kcr) is a newly discovered posttranslational modification epigenetic pattern that may affect gene expression and is linked to diseases causally. We collected blood samples from 11 SLE individuals and 36 healthy subjects. Then, we used highly sensitive liquid chromatography-mass spectrometry technology to carry out proteomics and quantitative crotonylome analysis of SLE peripheral blood mononuclear cells in this investigation, which indicated the unique etiology of SLE. Finally, we verified the expression of critical protein in the leukocyte extravasation pathway by online database analysis and Western blot. There were 618 differentially expressed proteins (DEPs), and 612 crotonylated lysine sites for 272 differentially modified proteins (DMPs) found. These DEPs and DMPs are primarily enriched in the leukocyte extravasation signaling pathway, such as MMP8, MMP9, and ITGAM. This is the first study of crotonylated modification proteomics in SLE. The leukocyte extravasation signaling pathway had a considerable concentration of DEPs and DMPs, indicating that this pathway may be involved in the pathogenic development of SLE.

Vitamin D Activates miR-126a-5p to Target GSK-3β and Alleviates Systemic Lupus Erythematosus in MRL/LPR Mice.

The etiology of systemic lupus erythematosus (SLE) is complex, and the disease is thus difficult to cure. In this regard, it has been established that SLE patients are characterized by differing levels of vitamin D-hydroxylation; however, the direct effects of vitamin D (VitD) in these patients remain unknown. Therefore, we investigated the effects and mechanisms of action of VitD in the context of SLE. The effects of VitD on MRL/LPR mice were studied by synthesizing glycogen synthase kinase-3β (GSK-3β)-interfering lentiviruses and transfecting with miR-126a-5p mimics. Changes in the body weight of mice were recorded for 6 weeks. Western blotting was performed to determine the levels of T-bet, GATA3, and GSK-3β protein expression, and qRT-PCR was performed to determine the levels of miR-126a-5p and GSK-3β mRNA expression. ELISA was performed to determine the levels of ANA, dsDNA, and snRNP/Sm in mice serum. GSK-3β and miR-126a-5p were expressed at high and low levels, respectively, in MRL/LPR mice. VitD (30 ng/kg) was found to reduce the expression of GSK-3β and increase miR-126a-5p expression, which targets GSK-3β. T-bet and GATA3 were found to be positively regulated by miR-126a-5p and VitD and negatively regulated by GSK-3β. The body weight of mice was not altered by VitD. ANA, dsDNA, and snRNP/Sm were positively regulated by miR-126a-5p and VitD and negatively regulated by GSK-3β. The effects of GSK-3β were enhanced in response to the inhibition of miR-126a-5p expression. VitD upregulated miR-126a-5p to target GSK-3β expression, thereby alleviating the SLE in MRL/LPR mice.

TRIM5 Promotes Systemic Lupus Erythematosus Through CD4(+) T Cells and Macrophage.

Systemic lupus erythematosus (SLE) is a typical autoimmune disease characterized by the involvement of multiple organs and the production of antinuclear antibodies. This study aimed to investigate the molecular mechanism of SLE. We retrieved genome-wide gene expression levels from five public datasets with relatively large sample sizes from the Gene Expression Omnibus (GEO), and we compared the expression profiles of peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls (HCs). The expression of seven target genes in PBMCs from 25 cases and 3 HCs was further validated by reverse-transcription quantitative PCR (RT‒qPCR). Flow cytometry was used for verifying the proportion of naive CD4(+) T cells and M2 macrophages in PBMCs from 5 cases and 4 HCs. We found 14 genes (TRIM5, FAM8A1, SHFL, LHFPL2, PARP14, IFIT5, PARP12, DDX60, IRF7, IF144, OAS1, OAS3, RHBDF2, and RSAD2) that were differentially expressed among all five datasets. The heterogeneity test under the fixed effect model showed no obvious heterogeneity of TRIM5, FAM8A1, and SHFL across different populations. TRIM5 was positively correlated with the remaining 13 genes. By separating patient samples into TRIM5-high and TRIM5-low groups, we found that up-regulated genes in the TRIM5-high group were mainly enriched in virus-related pathways. Immune cell proportion analysis and flow cytometry revealed that naive CD4(+) T cells were significantly decreased while M2 macrophages were increased in the SLE group. TRIM5 expression levels were negatively correlated with naive CD4(+) T cells but positively correlated with M2 macrophages. Our data indicated that TRIM5 might be a key factor that modulates SLE etiology, possibly through naive CD4(+) T cells and M2 macrophages.

Peningkatan Kepatuhan Minum Obat Pasien Lupus Eritematosus Sistemik

Systemic Lupus Erythematosus (SLE) is an important systemic autoimmune disease. Women are ten times more at risk of developing LES than men. The etiology of SLE is not fully understood and the pathophysiology involves genetic, immunological, endocrine and environmental factors. SLE is a chronic disease with periods of remission and relapse, so it requires different management and a long time. Medication adherence is required so that treatment goals can be achieved. Medication adherence rates in people with lupus have been reported from various studies to be 31.7-45.9%. Non-adherence to treatment for SLE causes an increase in visits to the emergency department and also hospitalization. There are two kinds of factors that influence medication adherence, intentional non-adherence and non-intentional non-adherence. Efforts are needed to improve and increase medication adherence by considering these both factors.

Systemic Lupus Erythematosus in Men: Brief Description of Clinical and Laboratory Findings

Background: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of nuclear autoantibodies, which can cause autoimmune complex formation and inflammation of multiple organs. It is known to affect women more frequently than men and is typically diagnosed during reproductive age, where the female-male ratio has been reported as high as 12:1. The etiology of SLE is not fully understood, but both genetic predisposition and environmental triggers are believed to be involved. Because of the multitude of presentations, manifestations, and serological abnormalities in patients with SLE, diagnosis can be challenging. Chronic discoid lupus and photosensitivity have been found in men with SLE as far as skin findings are concerned, there is less joint involvement in these patients, however, severe systemic findings predominate, such as serositis, pleurisy, central nervous system involvement with the presence of seizures. , thrombotic events and lupus nephropathy of the acute proliferative glomeruonephritis variety, serologically there is no consensus yet, nor in the specific clinical characteristics but the presence of anti-dsDNA anti-Sm antibodies and anticardiolipin antibodies is also frequently found. Therapeutic approaches predominantly involve immunomodulation and immunosuppression and are targeted to be the specific organ manifestation, with the aim of achieving low disease activity. Conclusion: We considered that although male patients with lupus are not commonly seen, the manifestations are life threatening, and timely diagnosis and treatment of the disease will lead to a better outcome for these patients.

Megamonas funiformis, Plasma Zonulin, and Sodium Intake Affect C3 Complement Levels in Inactive Systemic Lupus Erythematosus.

The etiology of systemic lupus erythematosus (SLE) remains unclear, with both genetic and environmental factors potentially contributing. This study aimed to explore the relationship among gut microbiota (GM), intestinal permeability, and food intake with inflammatory markers in inactive SLE patients. A total of 22 women with inactive SLE and 20 healthy volunteers were enrolled, and dietary intake was assessed through 24-h dietary recalls. Plasma zonulin was used to evaluate intestinal permeability, while GM was determined by 16S rRNA sequencing. Regression models were used to analyze laboratory markers of lupus disease (C3 and C4 complement and C-reactive protein). Our results showed that the genus Megamonas was significantly enriched in the iSLE group (p < 0.001), with Megamonas funiformis associated with all evaluated laboratory tests (p < 0.05). Plasma zonulin was associated with C3 levels (p = 0.016), and sodium intake was negatively associated with C3 and C4 levels (p < 0.05). A combined model incorporating variables from each group (GM, intestinal permeability, and food intake) demonstrated a significant association with C3 complement levels (p < 0.01). These findings suggest that increased Megamonas funiformis abundance, elevated plasma zonulin, and higher sodium intake may contribute to reduced C3 complement levels in women with inactive SLE.

Deciphering novel common gene signatures for rheumatoid arthritis and systemic lupus erythematosus by integrative analysis of transcriptomic profiles.

Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE) are the two highly prevalent debilitating and sometimes life-threatening systemic inflammatory autoimmune diseases. The etiology and pathogenesis of RA and SLE are interconnected in several ways, with limited knowledge about the underlying molecular mechanisms. With the motivation to better understand shared biological mechanisms and determine novel therapeutic targets, we explored common molecular disease signatures by performing a meta-analysis of publicly available microarray gene expression datasets of RA and SLE. We performed an integrated, multi-cohort analysis of 1088 transcriptomic profiles from 14 independent studies to identify common gene signatures. We identified sixty-two genes common among RA and SLE, out of which fifty-nine genes (21 upregulated and 38 downregulated) had similar expression profiles in the diseases. However, antagonistic expression profiles were observed for ACVR2A, FAM135A, and MAPRE1 genes. Thirty genes common between RA and SLE were proposed as robust gene signatures, with persistent expression in all the studies and cell types. These gene signatures were found to be involved in innate as well as adaptive immune responses, bone development and growth. In conclusion, our analysis of multicohort and multiple microarray datasets would provide the basis for understanding the common mechanisms of pathogenesis and exploring these gene signatures for their diagnostic and therapeutic potential.

Assessment of miR-146a Gene Polymorphisms in Patients with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a multifactorial chronic autoimmune disease, with a wide spectrum of effect. The main feature of the disease is the production of a wide variety of autoantibodies as a result of immune tolerance loss. The work aims to evaluate the miRNA-146a gene polymorphism potential association with disease activity and chronicity changes in SLE patients. The study included 100 SLE patients and 50 matched controls. The systemic lupus erythematosus disease activity index (SLEDAI) was assessed. The single nucleotide polymorphism (SNP) of miR-146a gene (rs2910164) polymorphism was assayed by polymerase chain reaction (PCR) and sequencing technique in patients and control. 100 SLE patients were all females and with a mean of age 31.3 ± 10 years (16-63years) and disease duration of 5.8 ± 3.7years (1 month to 15 years). Most clinical manifestations presented in patients were 52% malar rash, 45% oral ulcers, 54% arthritis, and 45% neurological disorder. Proteinuria, ESR, creatinine and AST were significantly higher (65% vs. 10%, 4.1±36.1 vs. 11.8±9.9 mm/hr, 0.62±0.11 vs. 0.70±0.14 mg/dl and 25.37±26.50 vs. 17.23±3.58 U/L respectively) while the PLT was significantly lower (231.9±88.8 vs. 282.3±67.3 103/mL) (p&lt; 0.001) among SLE patients as compared to control. There were no significant variations in all study parameters across miRNA-146a genotypes (p greater than 0.05). There was a significant association of the homozygote GG genotype (66.7%) with the active SLE state (p=0.013). In conclusion, the results suggest a risk effect for the female gender and adult at a young age in the etiology of SLE. The miRNA-146a GG genotype is associated with increasing the disease activity and miRNA-146a polymorphism is not associated with the risk in SLE.

LncRNA GAS5 as an Inflammatory Regulator Acting through Pathway in Human Lupus.

To investigate the contribution of GAS5 in the pathogenesis of SLE. Systemic Lupus Erythematosus (SLE) is characterized by aberrant activity of the immune system, leading to variable clinical symptoms. The etiology of SLE is multifactor, and growing evidence has shown that long noncoding RNAs (lncRNAs) are related to human SLE. Recently, lncRNA growth arrest-specific transcript 5 (GAS5) has been reported to be associated with SLE. However, the mechanism between GAS5 and SLE is still unknown. Find the specific mechanism of action of lncRNA GAS5 in SLE. Collecting samples of the SLE patients, Cell culture and treatment, Plasmid construction, and transfection, Quantitative real-time PCR analysis, Enzyme-linked immunosorbent assay (ELISA), Cell viability analysis, Cell apoptosis analysis, Western blot. In this research, we investigated the contribution of GAS5 in the pathogenesis of SLE. We confirmed that, compared to healthy people, the expression of GAS5 was significantly decreased in peripheral monocytes of SLE patients. Subsequently, we found that GAS5 can inhibit the proliferation and promote the apoptosis of monocytes by over-expressing or knocking down the expression of GAS5. Additionally, the expression of GAS5 was suppressed by LPS. Silencing GAS5 significantly increased the expression of a group of chemokines and cytokines, including IL-1β, IL-6, and THFα, which were induced by LPS. Furthermore, it was identified the involvement of GAS5 in the TLR4-mediated inflammatory process was through affecting the activation of the MAPK signaling pathway. In general, the decreased GAS5 expression may be a potential contributor to the elevated production of a great number of cytokines and chemokines in SLE patients. And our research suggests that GAS5 contributes a regulatory role in the pathogenesis of SLE, and may provide a potential target for therapeutic intervention.

Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization.

Previous studies have reported that a few inflammatory cytokines have associations with systemic lupus erythematosus (SLE)-for example, IL-6, IL-17, and macrophage inflammatory protein (MIP). This Mendelian randomization was conducted to further assess the causal correlations between 41 inflammatory cytokines and SLE. The two-sample Mendelian randomization utilized genetic variances of SLE from a large publicly available genome-wide association study (GWAS) (7,219 cases and 15,991 controls of European ancestry) and inflammatory cytokines from a GWAS summary containing 8,293 healthy participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were simultaneously applied to strengthen the final results. The results indicated that cutaneous T cell-attracting chemokine (CTACK) and IL-17 may be suggestively associated with the risk of SLE (odds ratio, OR: 1.21, 95%CI: 1.04-1.41, p = 0.015; OR: 1.37, 95%CI: 1.03-1.82, p = 0.029). In addition, cytokines including beta nerve growth factor, basic fibroblast growth factor, IL-4, IL-6, interferon gamma-induced protein 10, monokine induced by interferon-gamma, MIP1b, stromal cell-derived factor-1 alpha, and tumor necrosis factor-alpha are suggested to be the consequences of SLE disease (Beta: 0.035, p = 0.014; Beta: 0.021, p = 0.032; Beta: 0.024, p = 0.013; Beta: 0.019, p = 0.042; Beta: 0.040, p = 0.005; Beta: 0.046, p = 0.001; Beta: 0.021, p = 0.029; Beta: 0.019, p = 0.045; Beta: 0.029, p = 0.048). This study suggested that CTACK and IL-17 are probably the factors correlated with SLE etiology, while a couple of inflammatory cytokines are more likely to be involved in SLE development downstream.

The emerging role of noncoding RNAs in systemic lupus erythematosus: new insights into the master regulators of disease pathogenesis.

Auto-immune diseases are a form of chronic disorders in which the immune system destroys the body's cells due to a loss of tolerance to self-antigens. Systemic lupus erythematosus (SLE), identified by the production of autoantibodies in different body parts, is one of the most well-known examples of these diseases. Although the etiology of SLE is unclear, the disease's progression may be affected by genetic and environmental factors. As studies in twins provide adequate evidence for genetic involvement in the SLE, other phenomena such as metallization, histone modifications, and alterations in the expression of noncoding RNAs (ncRNAs) also indicate the involvement of epigenetic factors in this disease. Among all the epigenetic alterations, ncRNAs appear to have the most crucial contribution to the pathogenesis of SLE. The ncRNAs' length and size are divided into three main classes: micro RNAs, long noncoding RNAs (LncRNA), and circular RNAs (circRNAs). Accumulating evidence suggests that dysregulations in these ncRNAs contributed to the pathogenesis of SLE. Hence, clarifying the function of these groups of ncRNAs in the pathophysiology of SLE provides a deeper understanding of the disease. It also opens up new opportunities to develop targeted therapies for this disease.

Evaluation of Interferon Alpha (IFN-α) in Women with Systemic Lupus Erythematosus in Iraq

Systemic Lupus Erythematosus (SLE) is a multifactorial chronic systemic autoimmune disease. It is characterized by a lack of immune tolerance to autoantigens such as nuclear antigens. The aim of the study is to assess the interferon-alpha (IFN-α) serum level in Iraqi patients with SLE and determine its potential relation to different clinical and laboratory parameters and disease activity. 100 SLE patients were all females and with a mean of age 31.3 ± 10 years (16-63years) and disease duration of 5.8 ± 3.7years (1 month to 15 years). The average of SLEDAI score ranged from 2 to 22 with a mean of (8.53 ±3.42). Proteinuria, ESR, creatinine and AST were significantly higher (65% vs. 10% and 0.62±0.11 vs. 0.70±0.14 mg/dl respectively) while the PLT was significantly lower (231.9±88.8 vs. 282.3±67.3 103/mL) (p&lt; 0.001) among SLE patients as compared to control. Serum levels of IFN-α were increased in the SLE patients compared to control, and no significant difference has been observed (208.7±530.0 vs. 63.7±34.8 pg/ml) respectively (P=0.245). Interferon-alpha showed a significant negative correlation with the SLE Disease Activity Index (SLEDAI) in the active and inactive groups. There were no significant variations in all study parameters across IFN-α serum levels (p greater than 0.05). In conclusion, the results suggest a risk effect for female gender and age in etiology of SLE. IFN-α could not be considered as biomarker or to have a risk effect in SLE patients or perpetuate the disease activity. No evidence for any correlation between the IFN-α serum level and any clinical manifestations or laboratory investigation of the disease in current study except for age and disease duration, which suggests them as a risk factor for increasing the IFN-α serum level.

Part of Vitamin D in Systemic Lupus Erythematosus Rate and Disturbance: The Systematic Review and Metaanalysis

Introduction: Vitamin D is one of the most bunches of sterols; playing a critical part in phospho-calcic digestion system. The change of 7-dehydrocholesterol to pre- vitamin D3 within the skin, through sun oriented bright B radiation, is the most source of vitamin D. Since lupus patients are more often than not photosensitive, the chance of creating vitamin D lack in is tall in this populace. In spite of the fact that confirmations appeared the intention between systemic lupus erythematosus (SLE) and vitamin D through which SLE can lead to lower vitamin D levels, it is additionally imperative to consider the plausibility that vitamin D insufficiency may have a causative part in SLE etiology. This paper analyzes existing information from different thinks about to highlight the part of vitamin D lack in SLE event and disturbance and the plausible adequacy of vitamin D supplementation on SLE patients. Method: This study using systematic review that search using keyword Vitamin D and Systemic Lupus Erythematosus in PubMed, Google Scholar and Science Direct. Result: After final screening the author analysize 4 articles. As in methods, the author summarize 4 articles. Conclusion: Confirmations appear that vitamin D plays an critical part within the pathogenesis and movement of SLE and vitamin D supplementation appears to improve incendiary and hemostatic markers; so, can progress clinical ensuing.

Skin lesions in systemic lupus erythematosus. Part 1: classification, etiology, pathogenesis

Skin and mucous membranes lesions in systemic lupus erythematosus (SLE) significantly impair the quality of life of patients, although they are not a formidable manifestation of the disease. Skin manifestations of SLE can occur both at the onset and on the late stage of the disease. Although skin and mucous membranes lesions are clearly grouped in the latest classification criteria for SLE, verification of the diagnosis requires a multidisciplinary approach. In the etiology of SLE, environmental factors, hormonal factors, and genetic predisposition play a role. Further research will reveal differences in subtypes of cutaneous lupus erythematosus and will facilitate the development of new therapies.

Identification of Diagnostic Biomarkers in Systemic Lupus Erythematosus Based on Bioinformatics Analysis and Machine Learning.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects several organs and causes variable clinical symptoms. Exploring new insights on genetic factors may help reveal SLE etiology and improve the survival of SLE patients. The current study is designed to identify key genes involved in SLE and develop potential diagnostic biomarkers for SLE in clinical practice. Expression data of all genes of SLE and control samples in GSE65391 and GSE72509 datasets were downloaded from the Gene Expression Omnibus (GEO) database. A total of 11 accurate differentially expressed genes (DEGs) were identified by the “limma” and “RobustRankAggreg” R package. All these genes were functionally associated with several immune-related biological processes and a single KEGG (Kyoto Encyclopedia of Genes and Genome) pathway of necroptosis. The PPI analysis showed that IFI44, IFI44L, EIF2AK2, IFIT3, IFITM3, ZBP1, TRIM22, PRIC285, XAF1, and PARP9 could interact with each other. In addition, the expression patterns of these DEGs were found to be consistent in GSE39088. Moreover, Receiver operating characteristic (ROC) curves analysis indicated that all these DEGs could serve as potential diagnostic biomarkers according to the area under the ROC curve (AUC) values. Furthermore, we constructed the transcription factor (TF)-diagnostic biomarker-microRNA (miRNA) network composed of 278 nodes and 405 edges, and a drug-diagnostic biomarker network consisting of 218 nodes and 459 edges. To investigate the relationship between diagnostic biomarkers and the immune system, we evaluated the immune infiltration landscape of SLE and control samples from GSE6539. Finally, using a variety of machine learning methods, IFI44 was determined to be the optimal diagnostic biomarker of SLE and then verified by quantitative real-time PCR (qRT-PCR) in an independent cohort. Our findings may benefit the diagnosis of patients with SLE and guide in developing novel targeted therapy in treating SLE patients.

The Role of IL-12 in the Aetiology of SLE and its Connection to HBV Infection in Iraqi Patients

Introduction: Systemic lupus erythematosus (SLE) is a significant social and public health issue because the medications used to treat it can only manage the symptoms and halt the progression of the disease, not totally cure it. The purpose of this study is to determine the association between the blood level of IL-12 and SLE, as well as its consequences, such as lupus nephritis (LN), and its active or dormant condition, in Iraqi patients.Method: The study enrolled 90 SLE patients from AL-Sadar teaching hospital, with 66(73.3%) developing lupus nephritis (LN) and 24(26.7%) without LN. Additionally, there were 60 (90.9%) and 6 (9.1) active patients. Only 48 of 90 individuals tested positive for HBsAg, whereas 42(46.6%) tested positive for HBV. Each participant donated 5 ml of blood for anti-dsDNA and IL-12 testing.Results: In SLE patients with LN, IL-12 serum levels were considerably higher than in those without LN(p = 0.05). Different levels of IL-12 were found in the LN groups. Serum IL-12 concentrations were considerably lower in patients with HBV-associated SLE (3.41±0.85 pg/ml), non-HBV-associated SLE (2.05±0.66 pg/ml), and healthy controls (0.53±0.28 pg/ml). WBC count, ESR, anti-ds antibody, and ANA levels were all elevated in lupus patients and in the active groups.Conclusion: Our research established that SLE patients have elevated IL-12 levels. IL-12 levels were significantly greater in SLE with LN as compared to SLE without LN, and they differed significantly between lupus nephritis classes II, IV, and V. Finally, significant differences in IL-12 levels were seen between HBV and non-HBV SLE patients.

The relation of CD4+CD25+Foxp3+ regulatory T cells concentration with disease activity and damage index in systemic lupus erythematosus.

Regulatory T cells (Treg) deficits, both quantitative and qualitative, are known to be possible triggers for the development of autoimmune disorders by causing T and B cells dysfunction. The contribution of Treg deficiency in the etiology of systemic lupus erythematosus (SLE) is still being debated. The aim of the present study is to evaluate the percentage of circulating CD4+CD25+Foxp3+ Treg cells in a cohort of Egyptian SLE patients and to correlate this value with the activity and damage index of these patients. 50 female patients with SLE together with an equal number of age- and sex-matched healthy controls were enrolled in the study. Flow cytometric determination of peripheral Treg cells was carried out for all participants by detecting the percentage of CD4+CD25+Foxp3+ cells to compare cases with the control group. Disease activity was assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), while disease damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI). Both indices were correlated with the percentage of CD4+CD25+Foxp3 T regulatory cells. CD4+CD25+Foxp3+ Treg cells percentage was significantly decreased in patients with SLE as compared to healthy controls. On correlating CD4+CD25+Foxp3+ Treg percentage with SLEDAI-2K, a significantly negative correlation was found. Also, there was a negative significant correlation between CD4+CD25+Foxp3+ Treg cells percentage and SLICC/ACR DI. On correlating SLEDAI-2K with damage index (SLICC/ACR DI), we found highly significant positive correlation. Our study showed impaired production of CD4+CD25+Foxp3+ Tregs in SLE patients, which can play a reciprocal role with some cytokines to affect the activity of the disease and organ damage. CD4+CD25+Foxp3+ Tregs cells should be the target to determine the clinical effectiveness of new therapy to modulate Tregs besides the traditional treatments.

Epigenetic Alterations in Immune Cells of Systemic Lupus Erythematosus and Therapeutic Implications.

Systemic lupus erythematosus (SLE) is an autoimmune disorder that is characterized by autoantibody production and dysregulated immune cell activation. Although the exact etiology of SLE remains unknown, genetic, hormonal, and complex environmental factors are known to be critical for pathologic immune activation. In addition to the inherited genetic predisposition, epigenetic processes that do not change the genomic code, such as DNA methylation, histone modification, and noncoding RNAs are increasingly appreciated to play important roles in lupus pathogenesis. We herein focus on the up-to-date findings of lupus-associated epigenetic alterations and their pathophysiology in lupus development. We also summarize the therapeutic potential of the new findings. It is likely that advances in the epigenetic study will help to predict individual disease outcomes, promise diagnostic accuracy, and design new target-directed immunotherapies.

CD4+ T Cells Promote IgG Production in MHC-Independent and ICAM-1-Dependent Manners in Pristane-Induced Lupus Mice

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and chronic inflammation. The etiology and pathogenesis of SLE are complicated in which dysfunction of CD4+ T cells is largely engaged. In this study, we investigated the manners of CD4+ T cells in antibody production in a lupus-like mouse model through peritoneal injection of pristane reagent. With the increase in total IgG/IgM and autoantibody production after 6 months, CD4+ T cells exhibited activated phenotypes with the elevated CD44, ICOS, OX40, and PD-1 expression. Pristane injection induced the increase in IgM levels in both wild-type and T cell-deficient TCRα−/− mice whereas IgG, IgG1, and IgG2a production was impaired. When adoptively transferring CD4+ T cells into T cell-deficient mice or coculturing CD4+ T cells and B cells in vitro, it was found that CD4+ T cells derived from pristane-treated mice could help the production of total IgG as well as IgG1/IgG2a in a more efficient manner both in vivo and in vitro. While MHC was dispensable for IgG production, ICAM-1 likely functioned as an attenuating factor for IgG production. Our study thus reveals that CD4+ T cells in pristane-treated mice play important roles in IgG production, which implies the critical roles in the induction of pathological autoantibodies in MHC-independent and ICAM-1-dependent manners.