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The Fas gene polymorphisms -670A/G (rs1800682) and -1377G/A (rs2234767) have been shown to be associated with systemic lupus erythematosus (SLE), but findings are not consistent. To clarify this point, a meta-analysis was performed. We searched PubMed, CNKI, CBM and Wanfang database. Meta-odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to combine the data by fixed/random effects models based on heterogeneity test. The statistical analyses were conducted using Stata software. A total of seven studies involving 759 cases and 820 controls were considered in this study and ethnicity-specific meta-analysis was performed on Caucasian and Asian population. In overall population, meta-analysis revealed a trend toward to an association between SLE and Fas -670 A allele (OR = 1.310, 95 %CI = 1.028 ~ 1.670, P = 0.029). Similar results were detected in recessive model (OR = 1.626, 95 %CI = 1.104 ~ 2.395, P = 0.014) and in homozygous genotypic contrast (OR = 1.728, 95 %CI = 1.049 ~ 2.848, P = 0.032). Stratification by ethnicity indicated a significant association between SLE and the Fas -670A/G polymorphism in Asian population when allelic contrast (OR = 1.331, 95 %CI = 1.066 ~ 1.662, P = 0.011), homozygous genotypic contrast (OR = 1.848, 95 %CI = 1.164 ~ 2.932, P = 0.009) and dominant model were performed (OR = 1.542, 95 %CI = 1.045 ~ 2.275, P = 0.029). Meta-analysis of the Fas -1377G/A polymorphism indicated a significant association between SLE and the G allele in overall population (OR = 1.277, 95 %CI = 1.004 ~ 1.624, P = 0.046). The results from this meta-analysis provide evidence for the association between the Fas -670A/G and -1377G/A polymorphism and the risk of SLE. However, further studies are needed to draw a definitive conclusion.

Many environmental and genetic factors have been contributed to the development of systemic sclerosis (SSc). To determine whether IL-10 gene polymorphisms are associated with SSc, we conducted a meta-analysis approach. A total of eight studies involving 1,034 SSc cases and 1,815 controls were obtained by electronic database, i.e. Embase, Blackwell, Scopus, China National Knowledge Infrastructure database, Chinese Biomedical database, Google searching. We analyzed three gene polymorphisms, including IL-10 -1082G/A (rs1800896), IL-10 -819C/T (rs1800871), IL-10 -3575T/A (rs1800890). The combined odds ratio (OR) with its 95% confidence interval (95% CI) was calculated using fixed or random effect models. We found that IL-10 819C allele might contribute to SSc susceptibility by fixed effect model and IL-10 3575A allele could be an important risk factor for SSc, especially in European descent. No significant heterogeneity were observed. Under random effect model, there was no evidence of statistically significant association between IL-10 1082G/A polymorphism and SSc. Publication bias was absent in all analyses. However, larger scale primary studies are required to further evaluate the IL-10 polymorphism and SSc.

The B-cell lymphocyte kinase (BLK) is a src-family protein tyrosine kinase specifically expressed in B-lineage cells that has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) and has been investigated in numerous ethnically diverse studies. However, genetic association studies that have examined the association between BLK gene variants and SLE have produced conflicting results. To shed further light on this issue, we performed a meta-analysis of the association between rs13277113, rs2248932 polymorphism and SLE in different ethnic groups. An updated literature-based meta-analysis of six original articles involving 20,271 control individuals and 11,796 subjects with SLE was conducted. Crude ORs with 95% CIs were used to assess the strength of association between rs13277113, rs2248932 polymorphism and SLE risk. Publication bias was estimated using Egger's linear regression test. The authors assessed the evidence of genotypic association using STATA Version 10.0. The combined overall odds ratio, calculated for SLE and the risk A-allele of rs13277113 was 1.416 (95% CI: 1.358, 1.477). An odds ratio of 1.264 (95% CI: 1.208, 1.322) was found for the T-allele of rs2248932. Significant associations of rs13277113 and SLE were observed for dominant model (AA + AG vs. GG, OR: 1.518; 95% CI: 1.411, 1.632), and recessive model (AA vs. AG + GG, OR: 1.553; 95% CI: 1.461, 1.651); so were rs2248932 and SLE for dominant model (TT + TC vs. CC, OR: 1.342; 95% CI: 1.233, 1.460), and recessive model (TT vs. TC + CC, OR: 1.338; 95% CI: 1.257, 1.424). All of these were conducted in fixed effects model as heterogeneity was not detected. Tests for bias revealed no evidence of biases. On the assessment of available evidence, the authors concluded that moderate evidence exists for an association between the BLK rs13277113, rs2248932 variants and SLE. Therefore, further research is warranted on the role of BLK polymorphisms in the etiology of SLE.

The aim of our meta-analysis was to quantitatively summarize the association of TYK2 gene polymorphisms with autoimmune and inflammatory diseases. 11 studies that included data from 21497 cases and 22647 controls were identified. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for six TYK2 gene polymorphisms (rs34536443, rs2304256, rs280523, rs280519, rs12720270 and rs12720356). Significant association was found in rs34536443 (C versus G: OR = 0.76, 95% CI = 0.69-0.84, P < 0.00001; GC + CC versus GG: OR = 0.78, 95% CI = 0.68-0.90, P = 0.0005; CC versus GG + GC: OR = 0.76, 95% CI = 0.28-2.05, P = 0.58; CC versus GG: OR = 0.74, 95% CI = 0.27-2.02, P = 0.56; GC versus GG: OR = 0.78, 95% CI = 0.68-0.90, P = 0.0006) and rs2304256 (A versus C: OR = 0.78, 95% CI = 0.70-0.87, P < 0.0001; CA + AA versus CC: OR = 0.69, 95% CI = 0.59-0.81, P < 0.0001; AA versus CC + CA: OR = 0.75, 95% CI = 0.66-1.00, P = 0.05; AA versus CC: OR = 0.64, 95% CI = 0.47-0.86, P = 0.003; CA versus CC: OR = 0.70, 95% CI = 0.60-0.83, P < 0.0001) in TYK2 gene, but not for the other polymorphisms (rs280523, rs280519, rs12720270, and rs12720356). This meta-analysis demonstrates that autoimmune and inflammatory diseases is associated with TYK2 gene rs34536443 and rs2304256 polymorphisms, but not rs280523, rs280519, rs12720270 and rs12720356.

Interleukin-21(IL-21) is the most recently discovered member of the type-I cytokine family. Structurally, IL-21 shows homology to IL-2, 4, and 15 proteins. It has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. Many previous studies have identified that IL-21 was associated with different autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. In addition, recent work has explored the role of IL-21 in systemic lupus erythematosus (SLE). Elevated expression of IL-21 was found in the sera of patients and mice with SLE. Moreover, association of IL-21 and IL-21R polymorphisms with susceptibility to SLE have been reported. All these findings suggest that IL-21 may have promise as a potential therapeutic target for SLE. In this review, we will discuss the biological features of IL-21, the IL-21 signaling and its potential role in SLE.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a recently identified proinflammatory cytokine of the TNF superfamily. Through activation of the fibroblast growth factor-inducible 14 (Fn14) receptor, TWEAK regulates cell proliferation, cell death and inflammation. The available evidences have indicated that TWEAK might be a target for therapeutic intervention in renal, vascular injury and neuropathy. Since renal, vascular and neuropsychiatric complications are frequently encountered in systemic lupus erythematosus (SLE)--a systemic autoimmune disease, TWEAK-Fn14 pathway may be implicated in the pathogenesis of SLE. In this review, we will discuss the TWEAK-Fn14 pathway and the therapeutic potential of modulating this pathway in SLE.

T-cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) was the first surface molecule that specifically identifies Th1 cells in both mice and human. Recently, identification of Galectin-9 as a ligand for TIM-3 has established the TIM-3-Galectin-9 pathway as an important regulator of Th1 immunity and tolerance induction. Many previous studies have demonstrated that TIM-3 influences chronic autoimmune diseases, such as multiple sclerosis and rheumatoid arthritis. In addition, association of TIM-3 polymorphisms with susceptibility to several autoimmune diseases has been identified. Recent work has explored the role of TIM-3 in systemic lupus erythematosus (SLE), and their results indicate that TIM-3 may represent a novel target for the treatment of SLE. In this review, we will discuss the TIM-3 pathway and the therapeutic potential of modulating the pathway in SLE.