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MiR-155 is a member of the microRNAs (miRNAs) family and regulates gene expression post-transcriptionally by binding to the 3'UTR of target mRNA. MiR-155 has a critical role in both innate and adaptive immunity. MiR-155 is aberrantly expressed in inflammatory autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, Sjögren's syndrome, systemic sclerosis, and inflammatory bowel disease. Functional studies suggest that miR-155 is involved in development of these diseases. In vitro and in vivo experiments have shown that inhibition of miR-155 can alter disease progression or ameliorate disease symptoms.A systematic review of relevant literatures published between January 1, 2005, and March 1, 2022 about miR-155 and its role in immune cells, autoimmune diseases was searched on PubMed, EMBASE, Google Scholar.In this review, we comprehensively discussed the effects of miR-155, including role of miR-155 in different downstream signaling, which then differently regulate immune cells expression and functions. Furthermore, miR-155-mediated dysfunction of immune cells contributed to development of inflammatory autoimmune diseases. Therefore, miR-155 is expected to be a therapeutic target for inflammatory autoimmune diseases.

We investigated plasma sirtuin-1 (SIRT1) levels in systemic lupus erythematosus (SLE) patients, and discussed potential of plasma SIRT1 as a biomarker for SLE.A total of 359 subjects, including 299 patients (89 SLE, 50 rheumatoid arthritis, 30 osteoarthritis, 30 gout, 38 Sjögren's syndrome, 20 ankylosing spondylitis, 30 mixed connective tissue disease, 12 systemic sclerosis) and 60 healthy controls were recruited. SIRT1 in plasma of SLE patients was detected by enzyme-linked immunosorbent assay. Relationship between SIRT1 levels, clinical, laboratory characteristics in SLE patients was discussed. Plasma SIRT1 to discriminate SLE from different rheumatic patients and healthy controls was assessed by receiver operating characteristic (ROC) curve analysis.SIRT1 levels were elevated in SLE patients compared with healthy controls (6.28 [5.89-6.68] vs 2.42 [2.10-2.74] ng/mL, P .001). SIRT1 concentration in plasma was significantly associated with disease activity (rCirculating SIRT1 was elevated in SLE, and might be a promising SLE diagnostic marker.

IL‐38 is a newly identified cytokine that belongs to the IL‐1 family. In our previous study, we found elevated plasma levels of IL‐38 in patients with systemic lupus erythematosus (SLE). However, the clear relationship of IL‐38 expression in plasma, peripheral blood mononuclear cells (PBMCs) and clinical and laboratory features needs elucidation. Additionally, we evaluated the possible role of IL‐38 in regulating production of inflammatory cytokines in PBMCs in vitro. A pristane‐induced murine lupus model was used to further demonstrate the effects of IL‐38 on cytokines in vivo and discuss the significance of IL‐38 in lupus development. The results showed that mRNA expression of IL‐38 in PBMCs of patients with SLE was elevated compared with volunteers, and expression of IL‐38 in both plasma and PBMCs was strongly related to clinical features, such as haematuria and proteinuria, and correlated with a SLEDAI score. Plasma levels of TNF‐α, IL‐1β, IL‐6 and IL‐23 were elevated in patients with SLE and were related to plasma levels of IL‐38. In vitro, PBMCs of patients with SLE stimulated with IL‐38 showed a decreased expression of the four inflammatory cytokines compared with PBMCs of patients without treatment. Interestingly, IL‐38 administration in lupus mice significantly reduced the development of lupus, such as reduced proteinuria, improved histological examinations of the kidneys and down‐regulated inflammatory cytokines. In conclusion, IL‐38 may suppress synthesis of pro‐inflammatory cytokines and therefore regulate lupus pathogenesis.

Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disorder. MASP2 is a mediator that plays an important role in complement system. As dysregulation of the complement system has been demonstrated to correlate with SLE pathogenesis, the role of MASP2 in lupus has not been widely discussed. In the present study, serum levels of MASP2 were evaluated in 61 lupus patients and 98 healthy controls by training cohort, and then a validation cohort including 100 lupus, 100 rheumatoid arthritis, 100 osteoarthritis, 100 gout, 44 Sjogren's syndrome, 41 ankylosing spondylitis patients confirmed the findings. Receiver operating characteristic (ROC) curve analysis determined the discriminatory capacity for serum MASP2. PCR methods tested the association of MASP2 gene polymorphisms (rs7548659, rs17409276, rs2273346, rs1782455 and rs6695096) and SLE risk. Impact of polymorphism on MASP2 serum levels was evaluated as well. Results showed that serum levels of MASP2 were significantly higher in lupus patients and correlated with some clinical, laboratory characteristics in the training cohort, and were much higher as compared to that in different rheumatic diseases patients in the validation cohort. Serum MASP2 showed a good diagnostic ability for lupus. Genotype frequencies and allele frequency of polymorphisms rs7548659, rs2273346 were strongly related to SLE risk, and genotypes of rs17409276, rs1782455, rs76695096 were significantly correlated with lupus genetic susceptibility. Interestingly, patients carrying GA genotype of rs17409276, TT, TC genotype of rs6695096 showed higher levels of serum MASP2. The findings suggested that MASP2 may be a potential disease marker for lupus, and correlate with SLE pathogenesis.

Association of signal transducer and activator of transcription 4 (STAT4) gene rs7574865, rs10168266 polymorphisms with systemic lupus erythematosus (SLE) risk remains unclear. A meta-analysis was conducted on the correlation between rs7574865, rs10168266 polymorphisms and SLE. Twenty-six studies were recruited in our study (17,389 patients and 29,273 controls). For rs7574865, results showed significant associations between T allele and SLE susceptibility in overall population, Asians and Europeans (OR=1.557, 95%CI: 1.505-1.611, P0.001; OR=1.557, 95%CI: 1.498-1.661, P0.001; OR=1.548, 95%CI: 1.474-1.625, P0.001). Significant associations of genotypes TT, GT, TT+TG and SLE risk were observed in general subjects, Asians and Europeans (all P0.001). Regarding rs10168266, increased T allele frequencies were detected in overall SLE cases and those from Asian origin (OR=1.532, 95%CI: 1.440-1.631, P0.001; OR=1.575, 95%CI: 1.445-1.717, P0.001). The overall data showed that TT genotype, CT genotype and TT+CT genotype were significantly correlated with SLE (all P0.001). In conclusion, the present study verified strong association of STAT4 gene rs7574865, rs10168266 polymorphisms and SLE susceptibility.

Previous studies reported that IL-38 was abnormally expressed in patients with systemic lupus erythematosus (SLE). However, the involvement of IL-38 in the pathophysiology of SLE remains unknown.The therapeutic potential of IL-38 was tested in pristane-treated wild-type (WT) and IL-38WT mice with pristane-induced lupus exhibited hepatomegaly, splenomegaly, severe kidney damages, increased lymphoproliferation, enhanced lymphoproliferation, and upregulated inflammatory cytokines, such as IL-6, IL-13, IL-17A, MIP-3α, IL-12p70, and IFNγ, and elevated levels of autoantibodies, such as ANA IgG, anti-dsDNA IgG, and total IgG. IL-38IL-38 regulates SLE pathogenesis. Furthermore, targeting IL-38 is critical in the treatment of SLE.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases. CD40 participates in inflammatory response, and promotes fibroblast proliferation, leading to occurrence and progression of SLE, RA. This study explores CD40 gene polymorphisms in SLE and RA patients from a Chinese Han population. Two hundred SLE patients, 340 RA patients, and 900 healthy controls were enrolled. Genomic DNA was extracted from peripheral blood, and six polymorphisms of CD40 gene (rs3765456, rs1569723, rs73115010, rs13040307, rs1883832, and rs4810485) were detected by KASP method. Frequencies of rs1569723 genotypes AA, AC, AA+AC were significantly higher in RA patients as compared to those in healthy controls (P = 0.049, P = 0.024, P = 0.022). Frequencies of genotypes CT, CC+CT of rs1883832, and GT, GG+GT of rs4810485 were significantly higher in RA patients as compared to those in healthy controls (P = 0.012, P = 0.018, P = 0.009, P = 0.015). RA patients carrying rs13040307 C allele and rs73115010 T allele showed increased number of swollen joints. Moreover, frequency of allele T of rs13040307 was lower in SLE patients with positive anti-dsDNA and hematuria as compared to that in patients without these parameters (P = 0.038, P = 0.045). There were increased frequencies of genotype TT, allele T for rs13040307 and lower frequencies of genotype TT, allele T for rs73115010 in lupus patients with myositis (all P

Interleukin-37 (IL-37) is an anti-inflammatory cytokine. In our former study, we found increased plasma IL-37 levels in systemic lupus erythematosus (SLE) patients. However, relationship between IL-37 levels and clinical laboratory characteristics of SLE patients has not been elucidated. In addition, association of

Correlation between soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) concentration, VEGFR1 gene polymorphisms and systemic lupus erythematosus (SLE) risk remains unclear. The present case–control study comprised 254 SLE patients, 385 other rheumatic diseases patients and 390 healthy controls. Serum levels of sVEGFR-1 were detected by enzyme-linked immunosorbent assay. Seven VEGFR1 genetic variants (rs2296188, rs9943922, rs2296283, rs7324510, rs9554322, rs9582036, rs9554320) were genotyped by KASP. Serum levels of sVEGFR-1 were up-regulated in SLE and positively correlated with disease activity. Furthermore, serum sVEGFR-1 presented a distinctive elevation in SLE in comparison with other rheumatic diseases. Frequencies of allele T of rs2296283 and allele G of rs9554322 were significant lower in SLE patients (P = 0.003, P = 0.004). Frequencies of genotypes TT of rs2296188 and rs2296283 were declined in patients compared with healthy controls (P = 0.039, P = 0.033). CC genotype of rs7324510 and rs9582036 was negatively correlated with SLE risk (OR = 0.538, OR = 0.508). Distribution of GG, GC, GG + GC genotypes of rs9554322 were different between SLE patients and healthy controls (P = 0.027, P = 0.036, P = 0.010). Moreover, frequency of TC genotype of rs7324510 was higher in SLE patients with lupus headache (χ2 = 9.924, P = 0.039) and frequency of TC genotype of rs9943922 was lower in patients with cylindruriain (χ2 = 7.589, P = 0.026). Frequencies of allele C of rs7324510 and allele T of rs9943922 were decreased in SLE patients with cylindruria and hypocomplementemia, respectively (χ2 = 4.195, P = 0.041, χ2 = 3.971, P = 0.046). However, frequency of allele C of rs9554322 was increased in SLE patients with pyuria (χ2 = 11.702, P = 0.001). In addition, SLE patients carrying GG, GC, CC genotypes for rs9554322 had higher levels of serum sVEGFR-1. In conclusion, serum sVEGFR-1 was elevated in SLE patients and may be a disease marker. VEGFR1 gene polymorphisms related to risk of SLE in a Chinese Han population.

This study aimed to discuss association between serum Angiopoietin2 (Ang2) levels, Ang2 gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility. It was carried out by 235 SLE, 342 other inflammatory autoimmune diseases patients and 380 healthy individuals. Serum Ang2 levels was examinated by ELISA, and Ang2 rs12674822, rs1823375, rs1868554, rs2442598, rs3739390 and rs734701 polymorphisms were genotyped using KASP. Increased Ang2 concentrations in SLE patients were observed compared with healthy controls and patients with other inflammatory autoimmune diseases. For allelic contrast, except for rs1823375 (P = 0.058) and rs2442598 (P = 0.523), frequencies of alleles for other polymorphisms were significantly different between SLE patients and controls. Genotypes for rs12674822 (TT), rs1868554 (TT, TA and TT+TA), rs734701 (TT) were negatively correlated with SLE susceptibility (OR = 0.564 for rs12674822; OR = 0.572, OR = 0.625, OR = 0.607 for rs1868554; OR = 0.580 for rs734701). Patients carrying rs1868554 T allele and rs3739390 G allele were more likely to develop hematuria (P = 0.039; P = 0.003). The G allele frequencies of rs12674822 and rs2442598 were higher in SLE patients with proteinuria (P = 0.043; P = 0.043). GC genotype frequency of rs3739390 was higher in patients with ds-DNA (+) (P = 0.024). In summary, SLE had increased serum Ang2, which may be a potential biomarker, and the polymorphisms correlated with SLE.

OBJECTIVES: Mannose binding lectin (MBL) gene single nucleotide polymorphisms have been associated with systemic lupus erythematosus (SLE) risk with inconsistent results. This study aimed to explore whether MBL2 A\B, A\C, A\D, A\O, L\H and Y\X polymorphisms affected SLE susceptibility. METHODS: A meta-analysis was performed on 20 studies, containing allelic contrast, additive, dominant and recessive models. Odds ratio (OR) was calculated to reflect the effect of association. RESULTS: A total of 64 pooled comparisons were conducted, including 7194 SLE patients and 7401 healthy controls. The meta-analysis inducted a significant association between allele B and SLE (OR = 0.766, 95% CI = 0.681-0.862, P

Background Interleukin-2 inducible T-cell kinase (ITK) is expressed in T cells, and plays an important role in autoimmune inflammatory diseases through regulating the balance of Th17/Treg. However, its role in human systemic lupus erythematosus (SLE) remains unclear. The present study aims to measure the activation status of ITK in T cells from SLE patients and healthy controls, and identify its possible correlation to disease severity. We also discuss the serum levels of Th17, Treg related cytokines including IL-17, IL-21, IL-22, IL-10, analyzing correlation between ITK and Th17/Treg related cytokines. Methods Peripheral blood samples were drawn from 42 patients with SLE and 43 healthy blood donors, and the phosphorylation of ITK protein was studied in T cells using flow cytometry. In addition, serum levels of Th17/Treg related cytokines were studied with enzyme-linked immunosorbent assay (ELISA). Results Percentages of CD4 + pITK + T cells, CD8 + pITK + T cells were higher in SLE patients compared with controls, and were positively related to disease activity, some clinical and laboratory parameters. Percentages of CD4 + pITK + T cells, CD8 + pITK + T cells were more prominent in active SLE patients compared with less active patients. Serum levels of Th17 and Treg related cytokines were higher in patients compared with controls. CD4 + pITK + T cells were related to levels of IL-17, IL-21. Conclusion These data indicate that increased ITK expression could act as a disease activity marker and as a risk factor for involvement in SLE, but it still needs further study to confirm.

BACKGROUND This study aimed to discuss the relationship between interferon regulatory factor (IRF)5 gene rs2004640 T/G polymorphism and systemic lupus erythematosus (SLE) susceptibility. METHODS A meta-analysis was calculated on the association between rs2004640 polymorphism and SLE by allelic contrast (T vs G), additive model (TT vs GG), recessive model (TT vs TG + GG) and dominant model (TT + TG vs GG). RESULTS A total of 28 comparisons were identified, including 11 228 SLE cases and 14 374 controls. Meta-analysis revealed a significant association between allele T and SLE in overall populations (odds ratio [OR] = 1.393, 95% CI: 1.276-1.522, P

Systemic lupus erythematosus (SLE) is an autoimmune disease. The friend leukemia insertion site 1 (Fli-1) belongs to the Ets family of transcription factors. Recent findings suggested that expression of Fli-1 was abnormal in SLE patients and lupus mice. In addition, functional analysis indicated that Fli-1 plays a key role in the development of this complex autoimmune disorder. Here, we review the updated evidence indicating the roles of Fli-1 in autoimmune lupus. Hopefully, the information obtained may result in a better understanding of the pathogenesis of the systemic autoimmune disease.

Background The aim of this study was to determine whether the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism confers susceptibility to systemic lupus erythematosus (SLE)/lupus nephritis (LN). Methods A meta-analysis was conducted on the association between the ACE I/D polymorphism and SLE/LN (when available) using: (i) the allelic contrast; (ii) the recessive; (iii) the dominant; and (iv) the additive models. Results A total of 27 relevant comparisons meeting the inclusion criteria were identified, involving 2718 SLE patients and 3655 controls. Meta-analysis showed a significant association between SLE and the allele D in overall populations (odds ratio [OR] = 1.25, 95% CI: 1.07-1.48, P = 0.004). Stratification by ethnicity indicated a strong association between the allele D and SLE in Asians (OR = 1.36, 95% CI: 1.05-1.75, P = 0.019). Meta-analysis also showed a significant association between SLE and the DD genotype in overall populations (additive model) (OR = 1.38, 95% CI: 1.05-1.83, P = 0.022). In addition, we found significant associations between the recessive model and SLE in overall populations, Asians and Europeans (OR = 1.44, 95% CI: 1.11-1.88, P = 0.007; OR = 1.69, 95% CI: 1.07-2.68, P = 0.024; and OR = 1.31, 95% CI: 1.06-1.62, P = 0.013, respectively). With respect to the association between ACE I/D gene polymorphism and LN risk, there was no significant association in either the overall populations or subpopulations. Conclusion The present study might suggest that ACE I/D polymorphism may be a genetic molecular marker to predict SLE, while this polymorphism may not correlate with LN susceptibility.

The H19 (rs2839698, rs3741219) and HOTAIR (rs920778) polymorphisms were related to many kinds of cancers. However, these polymorphisms have been scarcely explored in different autoimmune diseases. Here, we aimed to examine the association of the polymorphisms with susceptibility to or protection against systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren’s syndrome (pSS) among Chinese Han patients. We conducted a case-control study including 800 patients (300 with SLE, 350 with RA, and 150 with pSS) and 350 healthy control individuals. The polymorphisms were specified from genomic DNA using TaqMan genotyping assay on a 7300 real-time reverse transcription polymerase chain reaction system. H19 rs2839698 was not associated with SLE susceptibility and was not associated with RA and pSS, respectively (P > 0.05). Similarly, we did not find significant differences of allele or genotype frequencies between SLE, RA, and pSS patients and healthy controls for H19 gene rs3741219 polymorphism (P > 0.05). In addition, no significant evidence was detected for the relationship of HOTAIR rs920778 polymorphism with risk of these diseases. Our results suggested that H19 rs2839698, rs3741219, and HOTAIR rs920778 polymorphisms may not be involved in the genetic background of SLE, RA, and pSS in Chinese.

Systemic lupus erythematosus (SLE) is complex autoimmune disease which involves various facets of the immune system. Signaling transducers and activators of transcription 1 (STAT1) belongs to the family of STAT transcription factors that mediate various biological responses. Recently, studies in both experimental animal models of lupus and patients with SLE have revealed expression and activation of STAT1 is closely associated with the pathogenesis of SLE. Moreover, increased production of interferons (IFNs) and aberrant activation of IFNs signaling, which is mechanistically linked to increased level of STAT1, are crucial for the development of SLE. Therefore, we will focus on the association of STAT1 and SLE based on recent understandings to render more information about the mechanisms of STAT1 might perform in. Hopefully, the information obtained will lead to a better understanding of the development and pathogenesis of systemic autoimmune diseases, as well as its clinical implications and therapeutic potential.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by abnormal production of autoantibodies and proinflammatory cytokines. The clear pathogenesis of SLE has not been fully elucidated. Cytokine-mediated immunity has been showed to be involved in the pathogenesis of SLE. The aim of this study was to investigate serum levels of cytokines (IL-19, IL-24, IL-26, IL-31, IL-32, IL-36) in SLE patients, in comparison with normal controls in a Chinese population. A total of 65 patients with SLE and 65 healthy volunteers were recruited for the current study. All serum levels of cytokines were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not significantly different from the normal controls (all p > 0.05). Serum levels of IL-19, IL-24, IL-26, IL-31, IL-32 and IL-36 in SLE patients were not markedly different from the normal controls. However, functional research should be discussed in future studies to elucidate the roles of these cytokines in SLE.

To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) risk, we surveyed studies on the association of the TNFSF4 rs2205960, rs1234315, rs844644, and rs844648 polymorphisms with SLE.A literature-based search was conducted to identify all relevant studies. A total of eight independent studies were identified and subsequently reviewed in the meta-analysis.The meta-analysis showed an association between the TNFSF4 rs2205960 polymorphism and SLE in all subjects [ odds ratio (OR) 1.327, 95% confidence interval (CI) 1.227-1.436, P0.001]. In a subgroup analysis by ethnicity, a significantly increased risk for SLE was associated with TNFSF4 rs2205960 T allele among patients of European (OR 1.254, 95% CI 1.185-1.328, P0.001) and Asian ethnicity (OR 1.425, 95% CI 1.352-1.501, P0.001). The meta-analysis of the rs1234315 polymorphism revealed no association between SLE and the rs1234315 T allele in all subjects (OR 1.167, 95% CI 0.874-1.558, P = 0.296), but the results of the subgroup analysis revealed significant association in subjects of Asian ethnicity (OR 1.386, 95% CI 1.318-1.458, P0.001). No association was found between the rs844644 and rs844648 polymorphisms and SLE.The results of our meta-analysis suggest that the TNFSF4 rs2205960 polymorphism may confer susceptibility to SLE in different populations and that the TNFSF4 rs1234315 polymorphism is associated with susceptibility to SLE in Asians.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complex genetic predisposing factors involved. ITGAM and FCγRIIIA are two kinds of immune complex clearance molecules. The variants in ITGAM and FCγRIIIA genes have been confirmed to be associated with SLE. The aim of this study is to investigate the association of mRNA expression levels of ITGAM and FCγRIIIA with SLE. Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine the expression levels of ITGAM and FCγRIIIA mRNA in peripheral blood mononuclear cells (PBMC) from 60 patients with SLE and 60 healthy controls. Flow cytometry was used to measure the expression level of ITGAM and FcγRIIIA from 30 SLE patients and 30 healthy controls. The expression levels of ITGAM mRNA was significantly decreased in SLE patients compared with healthy controls (P = 0.007). Patients with arthritis had higher ITGAM mRNA level than those without arthritis (P = 0.029). The expression level of FCγRIIIA mRNA in SLE patients was significantly lower than that of healthy controls (P = 0.001). Decreased expression level of FCγRIIIA mRNA was also found in patients with LN compared with those without LN (P = 0.015). The level of ITGAM mRNA in patients with anti-SSB positive, anti-RNP positive, complement reduction and increased IgG was significantly reduced. No significant correlation was found between ITGAM and FcγRIIIA mRNA expression level in SLE patients (r = -0.019, P = 0.882). Expression of ITGAM protein in T cells, neutrophil and monocyte of SLE patients was significantly lower than healthy controls (P0.05). For FcγRIIIA protein expression in monocyte and NK cells, there were no significant difference between SLE patients and healthy controls (P0.05). The altered expression levels of ITGAM and FCγRIIIA mRNA in SLE patients and their correlations with clinical data suggest that ITGAM and FCγRIIIA may play a role in this disease.

Objective: The interleukin-10 (IL-10) gene polymorphism (–1082A/G) has been shown to be associated with systemic lupus erythematosus (SLE), but findings are not consistent across studies. The aim of our meta-analysis was to assess the association between the –1082A/G polymorphism in the IL-10 gene and SLE. Methods: We searched all publications on the association between the IL-10 (−1082A/G) polymorphism and SLE in PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI) and Wanfang (Chinese). Meta-analysis was conducted using software Stata version 10.1. Meta-odds ratios (ORs) and 95% confidence intervals (CIs) based on fixed-/random-effects models depended on Cochran’s Q-statistic and I2 values. Results: A total of 17 studies with 2396 cases and 3653 controls were included in this meta-analysis. Meta-analysis was performed for genotypes GG versus AA, GG + AG versus AA, GG versus AG + AA, and G allele versus A allele. Significant differences were found in genotype distribution between SLE and normal controls in whole-population GG versus AA (OR = 1.428, 95% CI = 1.006–2.208). Similar results were detected in the dominant genetics effect of the G allele (OR = 1.202, 95% CI = 1.030–1.403). No significant association was found in allele distribution in whole-population G versus A (OR = 1.125, 95% CI = 0.998–1.269). In subgroup analysis by ethnicity, significant association was found when GG + AG versus AA was performed in a European population (OR = 1.240, 95% CI = 1.022–1.503) and GG versus AG + AA was performed in an Asian population (OR = 3.596, 95% CI = 1.389–9.311). Significant association was found between genotype distribution in Asians (OR = 4.491, 95% CI = 1.552–13.000). Publication year was detected as the source of heterogeneity. In the stratified analysis by publication year, the pooled OR was 1.049 (95% CI = 0.940–1.171; Pheterogeneity = 0.431; I2 = 0.4%) in subgroup 1 (publication years 1999–2004). No significant association was found between the IL-10 (−1082 G) allele and SLE in subgroup 1 ( Z = 0.85, p = 0.431). In subgroup 2 (publication years 2005–2011), the pooled OR was 1.327 (95% CI = 1.125–1.565; Pheterogeneity = 0.143; I2 = 35.8%). Significant association was found between the IL-10 (−1082 G) allele and SLE ( Z = 3.36, p = 0.001). Conclusions: This meta-analysis demonstrates the association between the IL-10 (−1082A/G) polymorphism and SLE. However, further studies are needed for a definitive conclusion.

The RANTES (regulated on activation normal T cell expressed and secreted) and MBL (mannose binding lectin) single-nucleotide polymorphisms have been repeatedly associated with systemic lupus erythematosus (SLE), but the findings are not consistent across studies. The aim of this study was to determine whether the functional RANTES-28, -403 and MBL2 A/O polymorphisms confer susceptibility to SLE in multiple ethnic populations. A meta-analysis was conducted (allelic contrast, the additive model, the dominant model and the recessive model) on RANTES with seven studies (four studies for RANTES-28: three Asian and one American studies; three studies for RANTES-403: two Asian and one European studies), MBL with eight studies (five European and three American studies). OR is used as a measure of the effect of the association in a fixed/random effects model. The meta-analysis indicated that none of the two polymorphisms in gene of the RANTES showed any significant association with SLE risk, respectively, except for the recessive model (OR = 1.24, 95 % CI: 1.01-1.52, P = 0.04) in all study subjects combined with the two polymorphisms. According to the MBL2 A/O polymorphism, the results indicated a significant association between the polymorphism and SLE in allelic contrast (OR = 0.83, 95 % CI: 0.73-0.93, P = 0.002). While stratified by ethnicity in European, no significant association was found. In summary, the present study suggests that the RANTES-28, -403 polymorphisms do not associate with SLE, but the MBL2 A/O polymorphism might associate with SLE.

Recently, evidence is emerging that inappropriate regulation of type 17 T helper cells (Th17) plays a fundamental role in the development of many autoimmune diseases including systemic lupus erythematosus (SLE). However, the role of Th17-related cytokines in SLE remains elusive. To further investigate the role and imbalance of Th17-related cytokines in the pathogenesis of SLE. A Quantitative RT-PCR Array (Human Th17 for Autoimmunity & Inflammation PCR Array) analyses were performed to study Th17-related genes expression in peripheral white blood cells of 25 new-onset patients with SLE and 15 healthy subjects. When gene expression for SLE patients was compared to the mean of normal controls, among the 84 target genes related to Th17 pathway, 7 (CXCL1, ICAM1, IL10, IL5, IL8, ISG20, JAK2,) were upregulated and 6 (CD28, CD40LG, S1PR1, IL17RE, IL23R, RORC) downregulated. However, comparisons of mRNA expression of Th17 related cytokines between lupus nephritis (LN) patients and SLE patients without nephritis (SLE non LN) showed no significant difference. In conclusion, SLE patients and normal controls showed different expression of a few genes in Th17 pathway, indicating that the pathway may be involved in the pathogenesis of SLE.

Interleukin-18 (IL-18), belongs to the IL-1 cytokine family, has a variety of effects on dendritic cell, T cell, natural killer cell. Previous studies have identified that IL-18 was associated with the pathogenesis of systemic lupus erythematosus (SLE), wherein elevated expression of IL-18 was found in the serum of patients, and IL-18 polymorphisms with susceptibility to SLE were reported, suggesting that IL-18 may be therapeutically relevant to SLE. In this article, we will discuss the role of IL-18 in the pathogenesis of and its therapeutic potential in SLE based on current understandings.

Systemic lupus erythematosus (SLE) is an autoimmune disease. Cytokine-mediated immunity plays an important role in the pathogenesis of SLE. TNF-like ligand 1A (TL1A) belongs to the TNF superfamily of cytokines and has been found to perform significantly in autoimmune diseases, such as rheumatoid arthritis and inflammatory bowel disease. To date, no study has discussed the expression levels of TL1A in SLE. We found that plasma levels of TL1A were significantly higher in newly diagnosed SLE patients compared with controls. Correlation analysis showed that plasma levels of TL1A were positively associated with SLE disease activity index. These data indicated that TL1A may play a role in SLE and may reflect the disease activity for SLE.

Emerging evidences were accumulated to support the view that aberrant interleukin-7 (IL-7) signaling might be associated with autoimmunity. Former studies demonstrated the single nucleotide polymorphism (SNP) rs6897932 C/T in the IL-7 receptor (IL-7R) gene was associated with susceptibility to autoimmune diseases, including multiple sclerosis and type I diabetes. Given these, this study was conducted to investigate whether an association existed between SNP rs6897932 and the susceptibility to systemic lupus erythematosus (SLE), a severe systemic autoimmune disease. In this context, 816 SLE patients and 816 controls from a Chinese population were recruited for this study, and the results showed that the major allele C of rs6897932 showed a higher frequency in SLE patients compared with controls (P = 0.039, C versus T); significant difference was also detected under a recessive model with regard to the distribution of genotype frequencies between SLE patients and controls (P = 0.041, CC versus CT + TT), which was not consistent with the results under a dominant model (P = 0.349, CC + CT versus TT). Moreover, association studies were also performed contraposing the relationship between the SNP rs6897932 C/T and lupus nephritis as well as 10 clinical features of SLE; however, no significant association signal was found regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of 11 sub-phenotypes. In conclusion, the major allele C of SNP rs6897932 may be associated with increased SLE risk in Chinese populations, and further studies are still encouraged to shed light on the true associations between SLE and its susceptibility genes with respect to IL-7R gene.

Hypoxia-inducible factor 1 (HIF-1) introduced the immune imbalance between Th17 and Treg cells, which may play an important role in the pathogenesis of systemic lupus erythematosus (SLE). The aim of the present study was to determine whether the HIF1A gene influences the susceptibility to SLE. A study on this relationship has not been conducted to date. A total of 3,793 subjects (1,497 SLE patients and 2,296 controls) were included in this study. The genotyping of five single-nucleotide polymorphisms (SNPs) (rs11549465, rs12434438, rs1957757, rs1951795, rs7143164) was determined by Sequenom MassARRAY technology. The statistical analysis was conducted using chi-square test. Odds ratio (OR) with 95 % confidence interval (CI) was calculated using unconditional logistic regression with adjustment of age and sex. The allele frequencies were not associated with the disease. No significant differences in genotype frequencies existed between the patients with SLE and the controls in all five SNPs. It is worth mentioning that the allele T at rs11549465, located at the exon sequence, revealed a trend but no significant difference towards the more frequent allele T in SLE than in controls (C versus T: OR = 1.206, 95 % CI = 0.972–1.495, p = 0.088). The genotype effects of recessive, dominant, and codominant models were observed; however, no significant evidence for association was detected. Our findings suggest that the gene polymorphisms of HIF1A might not contribute to SLE susceptibility in the Chinese population. However, further studies are needed on an independent cohort from different genetic backgrounds to confirm HIF1A as an SLE genetic factor.

Systemic lupus erythematosus (SLE) is a severe multi-system autoimmune disease, whereas interferon regulatory factor (IRF) 5 belongs to the family of transcription factors that modulate immune system activities. Recently, many lines of investigations suggested that IRF5 gene polymorphisms are closely associated with the disease onset of SLE. Indeed, expressed in B cells, dendritic cells (DCs), monocytes and macrophages, IRF5 could significantly affect these immune cells participating in the pathogenesis of SLE, and numerous studies implied that this transcription factor is mechanistically linked to the disease progression. Here, we comprehensively review the updated evidence indicating the roles of IRF5 in autoimmune lupus. Hopefully, the information obtained will lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for the systemic autoimmune disease.

A great many studies have investigated the − 1082G/A polymorphism (rs1800896) in the interleukin-10 gene (IL10) with SLE susceptibility, but the results are inconsistent and inconclusive. The aim of this meta-analysis was in order to more precisely estimate the relationship. The databases of Pubmed and Web of Science updated to Oct, 2012 were retrieved. Odds ratio (OR) and corresponding 95% confidence interval (95%CI.) as effect size were calculated by fixed-effect model. Analysis for allele contrast of stratification by ethnicity in either Asian or Caucasian, as well as in overall population indicated no significant association (Overall: OR 1.096, 95%CI. 0.995–1.207; Asian: OR 1.204, 95%CI.: 0.944–1.535; Caucasian: OR 1.075, 95%CI.: 0.961–1.202). Analysis for recessive model showed no association in overall populations and in Caucasian (Overall: OR 1.135, 95%CI.: 0.945–1.362; Caucasian: OR 1.069, 95%CI.: 0.882–1.296), but significant association in Asian (OR: 2.848; 95%CI.: 1.194–6.791). Analysis for dominant model indicated that the variant G allele carriers (GG + GA) may have increased the risk of SLE when compared with the homozygote AA in overall populations and in Caucasian (Overall: OR 1.203, 95%CI.: 1.029–1.407; Caucasian: OR 1.233, 95%CI.: 1.014–1.499), but not in Asian (OR: 1.154; 95%CI.: 0.856–1.557). Significant association was found by using homozygote contrast model in overall populations and Asian (Overall: OR 1.303, 95%CI.: 1.031–1.648; Asian: OR 3.206, 95%CI.: 1.241–8.284), while no association was found in Caucasian (OR: 1.209; 95%CI.: 0.940–1.556). The results provided evidence for the association between the IL10 − 1082G/A polymorphism and the risk of SLE. To confirm these findings, more case–control studies with subtle study design based on adequately sized populations are required.

MicroRNAs (miRNAs) are a group of approximately 20–22-nucleotide-long non-coding RNAs that repress target gene expression through mRNA degradation and translation inhibition. MiRNA (miR)-146a, located in the second exon of the LOC285628 gene on human chromosome 5, is a negative regulator in immune and inflammatory responses. Studies have indicated that miR-146a is associated with the pathogenesis of several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjogren’s syndrome. In this review, emphasis will be laid on the recent progress in the functional roles of miR-146a in these autoimmune diseases.

C-Jun has been proved as playing an important role in the pathogenesis of tumors, as a main component of Activator protein 1 and c-Jun gene polymorphisms are associated with colorectal cancer. However, the relationship between the c-Jun gene polymorphism and the susceptibility to systemic lupus erythematosus (SLE) has not been known. Our purpose is to evaluate whether the c-Jun gene polymorphism (SNP rs3748814) is associated with susceptibility to SLE in a Chinese population. In this study, we enrolled 502 SLE patients and 652 healthy controls. The c-Jun polymorphism (rs3748814) was specified from genomic DNA using the TaqMan genotyping assay on a 7300 real-time reverse transcription polymerase chain reaction system. We found that the frequency of the A/G genotype in SLE patients was lower than in healthy controls, whereas the frequency of the G/G genotype was significantly higher in SLE patients than in healthy controls (A/G vs. G/G p = 8.670e-08, odds ratio [OR] = 0.290, 95% confidence interval [CI] = 0.184-0.456). In addition, the frequency of allele A in the patients group was significantly lower than in the control group (A vs. G p=5.221e-09, OR = 0.308, 95% CI = 0.212-0.466). The distribution of genotype and allele frequency in SLE patients with lupus nephritis (LN) compared with SLE patients without LN was not statistically significant (A/G vs. G/G p = 0.744, OR = 1.157, 95% CI=0.481-2.785; A vs. G p = 0.748, OR = 1.152, 95% CI = 0.486-2.734; A/A+A/G vs. G/G p = 0.744, OR = 1.157, 95% CI = 0.481-2.785). Furthermore, we did not find any significant association between other clinical features and genotypes. Our findings suggest that the c-Jun polymorphism (rs3748814) may be significantly associated with the susceptibility to SLE in a Chinese population.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Immune complex, autoantibodies and autoreactive lymphocytes are involved in manifestations of SLE. Recently, investigations have indicated that expression of the transcription factor cAMP responsive element modulator (CREM) is abnormal in T cells and might play an important role in the pathogenesis of SLE. CREM has much influence on the promoters, such as IL-2, c-fos, TCR ζ, and SYK. Moreover, activity of CREM itself has been demonstrated, particularly with an auto-regulatory feedback mechanism. Therefore, we will discuss the association of CREM and SLE based on current knowledge to unravel the mechanism of CREM performance.

Systemic lupus erythematosus is an autoimmune disease attributing to a combination of genetic and environmental factors. Abnormal expression/function of type I interferons has been demonstrated with the pathogenesis of SLE, especially IFN-α, which can be regulated by IFN regulatory factor 7 (IRF7). Single nucleotide polymorphisms (SNPs) near/in IRF7 have been substantiated related to onset of SLE, moreover, regulation of IRF7 expression/function has been found important in SLE. Therefore, we will discuss the association of IRF7 and SLE based on recent understandings to render more information about the mechanisms of IRF7 might perform in.

Leptin, the product of ob gene, is a 16-kDa nonglycosylated peptide hormone produced by adipocytes that regulates appetite and energy expenditure at the hypothalamic level. As is known to be a satiety factor that can regulate body weight by inhibiting food intake and stimulating energy expenditure, leptin is a pleiotropic hormone whose multiple effects include regulation of endocrine function, reproduction and immunity. Since leptin has been considered to be a pro-inflammatory cytokine, investigations of leptin in the pathogenesis of autoimmune diseases have been detected, such as systemic lupus erythematosus, rheumatoid arthritis and osteoarthritis. Recently, the role of leptin in the modulation of immune response and inflammation has been discussed in the autoimmune diseases increasingly but less in systemic lupus erythematosus (SLE). Therefore, this article will focus on the current understanding of the role of leptin with such similar pathogenic mechanism in SLE in order to provide insights which may assist in the development of leptin-based approaches for the treatment of SLE.