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Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the function changes of SNPs in the P2X7R, which affect the ATP-P2X7R-IL-1β signaling pathway with high uric acid, remained unknown. We aimed to explore the association between the functional change of the P2X7R containing the Ala348 to Thr polymorphism (rs1718119) and the pathogenesis of gout in the human P2X7 gene (P2RX7). First, 270 gout patients and 70 hyperuricemic patients without a history of gout attack within 5 years were recruited in this study. In addition, in functional studies, changes in ATP-induced pore formation were assessed in HEK-293T cells overexpressing different mutants in P2RX7, the effect on P2X7R-NLRP3-IL-1β pathway activation was explored in THP-1 cells overexpressing them. The gout-sensitivity allele at rs1718119 was A. The AA and AG genotypes exhibited a higher risk of gout. Furthermore, Ala348 to Thr increased P2X7-dependent ethidium+ bromide uptake. More importantly, Ala348 to Thr significantly upregulated the IL-1β and NLRP3 levels compared to the wild type. We suggest that genetic variability in the P2X7R containing the Ala348 to Thr polymorphism may be confers a gain-of-function effect with susceptibility to the development of gout.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complex genetic predisposing factors involved. PU.1 is an important member of the ETS transcription factors family which has diverse functions such as regulating the proliferation, differentiation of immune cells and multiple inflammatory cytokines. Previous studies preliminary explored the relation between PU.1 and SLE. To further explain the potential role of PU.1 in the pathogenesis of SLE, 40 SLE patients and 20 age-sex matched healthy controls (HC) were recruited in this study. Flow cytometry was used to test the percentages of CD4+PU.1+T cells in peripheral blood mononuclear cells (PBMCs) from patients with SLE and HC. Expression levels of PU.1 mRNA in CD4+T cells from SLE patients and HC were analyzed by real-time transcription-polymerase chain reaction. Expression levels of plasma IL-1β, IL-9, IL-18, IL-6, IFN-α, TNF-α, IL-10 and TGF-β1 were measured by enzyme-linked immunosorbent assay. The percentage of CD4+PU.1+T cells in PBMCs from patients with SLE was significantly higher than that from HC (P 0.05). Associations of PU.1 mRNA expression in CD4+T cells with major clinical and laboratory parameters of SLE patients were also analyzed, but no significant correlations were found. Consistent with previous studies, SLE patients had increased IL-1β, IL-18, IL-6, IFN-α, TNF-α and IL-10 plasma concentrations than HC (P

Gout is a common disease of inflammatory arthritis caused by hyperuricemia and the deposition of MSU crystals. Our previous study has shown that ATP action on P2X7R could be the second signal to induce the onset of gouty arthritis. However, the biological function changes of SNPs in the P2X7R, which affect the ATP-P2X7R-IL-1β signaling pathway with high uric acid, remained unknown. To further research P2RX7 gene variant (encoded by the SNP as rs1718119) polymorphism association between the gout susceptibility and the functional effect, 270 patients with gout and 70 hyperuricemia patients without history of gout flare (over 5-years course) were recruited in this study. The current study first time analyzed the genotyping study in genomic DNA samples from gout and hypeluricemia patients, then flow cytometry was used to test the transfected Ala348to Thr mutant in HEK-293T cells. Expression levels of IL-1β, NLRP3, ASC, caspase-1 mRNA in THP-1 cells were analyzed by quantitative real-time polymerase chain reaction. Expression levels of IL-1β were measured by enzyme-linked immunosorbent assay. The gout-sensitivity allele at rs1718119 was A. The AA and AG genotypes exhibited a higher risk of gout and the gout-sensitivity allele at rs1718119 was A. Moreover, Ala348to Thr increased P2X7-dependent ethidium+ bromide uptake. What’s more, Ala348 to Thr significantly up-regulated the serum and mRNA levels of IL-1β compared with wild type (P=0.0007;P=0.0334,respectively). Expression levels of NLRP3 mRNA in cells with Ala348 to Thr also showed a higher level than wild type(p=0.0003). However, no statistical significance were found in the mRNA expression of ASC and caspase-1 between Ala348to Thr and wild type in all three groups(P＞0.05). Our study revealed that the biological function changes of one SNP (rs1718119) mutation affected the ATP-P2X7R-IL-IL-1β signaling pathway with high uric acid. And, both rs1718119 was dominant gene. The genetic variability of the P2X7R rs1718119 gene might, in part, be associated with susceptibility for gout onset.

Background The objectives of this study were to assess the maintenance of effect of duloxetine 60 mg once-daily (QD) in Chinese patients with chronic pain due to osteoarthritis (OA) of the knee or hip and to provide additional long-term safety data. Methods This was an open-label, extension phase of a randomized, double-blind, placebo-controlled clinical trial. Eligible patients were outpatients who met the American College of Rheumatology clinical and radiographic criteria for OA with a rating ≥4 on Brief Pain Inventory (BPI) 24-h average pain. After completing the 13-week placebo-controlled phase, patients originally assigned to placebo were titrated to duloxetine 60 mg QD (PLA_DLX), whereas patients originally assigned to duloxetine 60 mg QD remained on the same dose of duloxetine (DLX_DLX) for another 13 weeks. The maintenance effect of duloxetine 60 mg QD during the extension phase was evaluated by a 1-sided 97.5% confidence interval (CI) of the baseline-to-endpoint change in the extension phase for patients who took duloxetine and reported ≥30% reduction in BPI average pain at the end of placebo-controlled phase (placebo-controlled phase duloxetine responders). Other BPI severity and interference items, as well as safety and tolerability, were assessed. Results Of 342 patients entering the extension phase, 162 (97.6%) DLX_DLX-treated patients and 157 (89.2%) PLA_DLX-treated patients completed this phase. Most patients (76.0%) were female. Mean age was 60.6 years. Mean BPI average pain was 5.5 at baseline of the placebo-controlled phase. Among 113 placebo-controlled phase duloxetine responders, mean change in BPI average pain during the extension phase was − 0.59 (from 2.47 to 1.88); the upper bound of the 1-sided 97.5% CI was − 0.31 and less than the pre-specified non-inferiority margin of a 1.5-point increase (p

The aim of this study was to investigate the B cell-associated transcription factors, Ets-1 and microRNA, miR-326 in systemic lupus erythematosus (SLE) patients, and their correlation with the pathogenesis of SLE. A total of 44 SLE patients and 20 healthy controls were enrolled in this research, all patients fulfilled the American College of Rheumatology classification criteria for SLE. The mRNA expression of Ets-1 and miR-326 in CD19+B cells from SLE patients were examined by qRT-PCR. The percentages of CD19+CD138+plasma cells were analyzed by Flow cytometry. We found decreased expression of Ets-1 mRNA in SLE patients compared with the healthy controls ([0.228 (0.145, 0.507)] vs [0.583 (0.452, 0.763)], p = 0.001),while increased expression of miR-326 mRNA in CD19+B cells SLE patients compared with the healthy controls([1.092 (0.457, 2.855)] vs [0.685 (0.274, 0.819)], p = 0.008). The percentage of CD19+CD138+plasma cells in SLE patients was higher than that of healthy controls (0.55 ± 0.21% vs 0.36 ± 0.21%, p = 0.002). Moreover, a negative correlation between expression of Ets-1 mRNA and miR-326 mRNA in CD19+B cells was detected (r = − 0.334, p = 0.027). A significant association between the occurrences of CD19+CD138+plasma cells and the levels of Ets-1 mRNA and miR-326 mRNA was observed (r = − 0.417, p = 0.005 and r = 0.482, p = 0.001, respectively). Our results suggest that miR-326 might promote B cells differentiation by targeting Ets-1, a negative regulator of B cells differentiation and therefore participate in the pathogenesis of SLE.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with complex genetic predisposing factors involved. PU.1 is an important member of the ETS transcription factors family which has diverse functions such as regulating the proliferation, differentiation of immune cells and multiple inflammatory cytokines. Previous studies preliminary explored the relation between PU.1 and SLE. To further explain the potential role of PU.1 in the pathogenesis of SLE, 40 SLE patients and 20 age-sex matched healthy controls (HC) were recruited in this study. Flow cytometry was used to test the percentages of CD4

B cells are recognized as key participants in various autoimmune diseases, including systemic lupus erythematosus (SLE). Although sets of transcription factors and cytokines are known to regulate B cell differentiation, the roles of microRNAs are poorly understood. Our previous study proved that microRNA-326 (miR-326) was markedly upregulated in SLE patients; however, the biological function of miR-326 during SLE pathogenesis remained unknown. In this study, we found that miR-326 overexpression in MRL/lpr mice led to B cell hyperactivity and severe SLE. Moreover, E26 transformation-specific-1 (Ets-1), a negative regulator of B cell differentiation, was identified as a target of miR-326. Therefore, a novel mechanism has been found in which the elevated miR-326 in B cells of SLE promotes plasmablast development and antibody production through downregulation of Ets-1.

Aim: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We assess the effect of tofacitinib + conventional synthetic disease-modifying anti rheumatic drugs (csDMARDs) on patient-reported outcomes in Chinese patients with RA and inadequate response to DMARDs. Methods: This analysis of data from the Phase 3 study ORAL Sync included Chinese patients randomized 4 : 4 : 1 : 1 to receive tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, placebo -g tofacitinib 5 mg twice daily, or placebo -g tofacitinib 10 mg twice daily, with csDMARDs. Placebo non-responders switched to tofacitinib at 3 months; the remaining placebo patients switched at 6 months. Least squares mean changes from baseline were reported for Health Assessment Questionnaire-Disability Index (HAQ-DI), patient assessment of arthritis pain (Pain), patient global assessment of disease activity (PtGA), physician global assessment of disease activity (PGA), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores, Short Form 36 (SF-36), and Work Limitations Questionnaire (WLQ), using a mixed-effects model for repeated measures. Results: Overall, 216 patients were included (tofacitinib 5 mg twice daily, n = 86; tofacitinib 10 mg twice daily, n = 86; placebo -g tofacitinib 5 mg twice daily, n = 22; placebo -g tofacitinib 10 mg twice daily, n = 22). At month 3, tofacitinib elicited significant improvements in HAQ-DI, Pain, PtGA, PGA and SF-36 Physical Component Summary scores. Improvements were generally maintained through 12 months. Conclusion: Tofacitinib 5 and 10 mg twice daily + csDMARDs resulted in improvements in health-related quality of life, physical function and Pain through 12 months in Chinese patients with RA.

The objective of this study is to analyze clinical manifestations, features of imaging, and laboratory assessment of patients with neuropsychiatric SLE (NPSLE) for better diagnosis and outcome prediction. One hundred eighteen NPSLE patients admitted to the Anhui Provincial Hospital in Hefei, China, between January 2006 and December 2016 were enrolled and analyzed retrospectively. All patients fulfilled the American College of Rheumatology revised classification criteria for SLE. Patients with NPSLE fulfilled the American College of Rheumatology (ACR) nomenclature and case definitions. All NPSLE patients underwent neurological investigations including MRI of nervous system, electroencephalograms, or CSF examination as part of the diagnostic evaluation of nervous system involvement. All statistical analyses were performed. According to different types of data, different statistical methods were used to determine factors associated with abnormal MRI among NPSLE patients. Statistical significance was defined as P value

This study aimed to systemically review the evidence regarding the relationship between the circulating blood osteoprotegerin (OPG) level and rheumatoid arthritis (RA), as well as the potential influential factors. Research related to plasma/serum OPG levels in RA patients and healthy controls were gathered using PubMed, EMBASE, and The Cochrane Library database (up to Jan. 1, 2017). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I 2, and publication bias was evaluated using a funnel plot and Egger's linear regression test. After searching databases, 443 articles were obtained, and 11 studies with 710 RA patients and 561 controls were finally included. Meta-analysis revealed that, compared with the control group, the OPG level was significantly higher in the RA group (P

Systemic lupus erythematosus (SLE) is associated with increased cardiovascular risk. This study aims to derive a more precise estimation on pulse wave velocity (PWV) level in patients with SLE and related factors. A literature search was performed using PubMed, EMBASE, and The Cochrane Library databases, studies published up to February 28, 2017, in English. Pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effect or random-effect model analysis. Heterogeneity test was performed by the Q statistic and quantified using I2; publication bias was evaluated using a funnel plot and Egger’s linear regression test. Of 156 studies found, 27 met eligibility criteria, and 14 studies were finally included in the meta-analysis. Meta-analysis revealed that the SLE group had significantly higher PWV levels than the control group; SMD = 0.56 and 95% CI (0.30-0.82). Subgroup analyses showed that body mass index (BMI), sample size, and disease duration were associated with PWV in patients with SLE. Overall, our study suggests that patients with SLE have a higher PWV level, and it is associated with BMI, sample size, and disease duration.

To explore the association of LEP and leptin receptor (LEPR) gene single‐nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.

In the present study, DNA methylation level of CD4+ T cells exposed to ultraviolet B (UVB) was investigated and its potential mechanisms were also explored. CD4+ T cells from 12 cases of healthy subjects and 33 cases of SLE patients were isolated and exposed to different dosages (0, 50, 100 mJ/cm2) of UVB. Further, SLE patients were divided into two groups: active SLE group (22 cases, SLEDAI scores >4) and inactive SLE group (11 cases, SLEDAI scores ≤4). DNA methylation was evaluated by the Methylamp™ Global DNA Methylation Quantification Ultra Kit. The mRNA and protein expression levels of DNA methyltransferases (DNMT1 and DNMT3A) were detected by real-time PCR and western blot, respectively. The levels of DNA methylation and DNMT3A mRNA in SLE patients were significantly decreased compared with those in healthy subjects at baseline. After different dosages of ultraviolet irradiation (0, 50 and 100 mJ/cm2), DNA methylation levels of CD4+ T cells were all reduced in a dose-dependent manner in three subgroups. Additionally, 100 mJ/cm2 ultraviolet irradiation in active SLE group contributed to a significant decrease of both DNA methylation and DNMT3A mRNA levels in CD4+ T cells. UVB exposure had no significant effects on expression levels of DNMT1 mRNA and protein and DNMT3A protein. UVB decreases DNA methylation level of CD4+ T cells in SLE patients probably via inhibiting DNMT3A mRNA expression level, which needs to be further explored.

Aim To investigate the efficacy and safety of technetium-99 conjugated with methylene diphosphonate (99Tc-MDP, Yunke Pharmaceutical industry) in the treatment of rheumatoid arthritis (RA). Methods A total of 120 patients with active RA were randomly divided into three groups: Group A (receiving oral meloxicam tablets); Group B (receiving intravenous drip of 99TC-MDP); Group C (receiving combination treatment of intravenous drip of 99Tc-MDP and oral meloxicam tablets). The main clinical and laboratory parameters were evaluated at baseline and after 14 days of therapy. Results After 14 days of treatment, American College of Rheumatology 20 response was 15.62%, 34.04% and 48.78% in the three groups, respectively. The incidence of adverse events in three groups were 3.13%, 8.51% and 9.76% respectly, and has no significant difference. In addition, biochemical markers of bone metabolism including bone alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP) and dickkopf-1 (DKK-1), all improved in the three groups, although more significant in Group B than Group A, and more significant in the combination group than monotherapy groups. Conclusion 99Tc-MDP has good efficacy and safety in the treatment of active RA patients; the benefit was more remarkable when 99Tc-MDP was combined with NSAIDs. 99Tc-MDP may also have potential to improve bone metabolism.

Autoimmune diseases contain a large number of pathologies characterized by various factors that contribute to a breakdown in self-tolerance. Cytokine-mediated immunity plays an essential role in the pathogenesis of varieties of autoimmune diseases. Recent studies reveal that interleukin-35 (IL-35), a newly identified cytokine of IL-12 family, is implicated in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), etc. In this review, we will discuss the biological features of IL-35 and summarize recent advances in the role of IL-35 in the development and pathogenesis of autoimmune diseases; the discoveries gained from these findings might translate into future therapies for these diseases.

Objective To evaluate the plasma levels of six adipokines, including chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin, in patients with SLE. Methods Ninety SLE patients and ninety control subjects were recruited, plasma adipokines levels were measured by enzyme-linked immunosorbent assay, and their associations with major clinical and laboratory indexes were analyzed. Results There were no significant differences in plasma chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin levels between SLE patients and controls. Further subgroup analyses by major clinical and laboratory indexes showed that plasma omentin-1 level was significantly lower in SLE patients without nephritis when compared with those patients with nephritis ( P = 0.002). Plasma chemerin, cathepsin-S levels in SLE patients without nervous system disorder were significantly lower in comparison with SLE patients with nervous system disorder ( P = 0.035, P = 0.029). No significant associations of other adipokines with any major clinical and laboratory indexes were observed. Conclusions Plasma levels of chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin in SLE patients were not markedly different from the normal controls. The presence of nephritis was connected with higher plasma omentin-1 levels in SLE patients, and the presence of nervous system disorder was associated with higher plasma chemerin, cathepsin-S levels in SLE patients. However, functional studies are awaited to further explore the potential roles of these cytokines in SLE.

The total glucosides of paeony (TGP) can inhibit inflammation and alleviate symptoms in autoimmune diseases. This study investigated the clinical and immunological consequences of TGP treatment in patients with primary Sjogren's syndrome (SS). We conducted a randomized, double-blinded, placebo-controlled clinical trial in 45 patients with primary SS. Patients were randomized at 2:1 ratio to either TGP group (n = 29) or placebo group (n = 16) and followed up for 24 weeks. The primary outocme was the European League Against Rheumatism Sjogren's Syndrome Patient Reported Index (ESSPRI). The secondary outcomes were stimulated and unstimulated salivary flow rate, Schirmer's test and erythrocyte sedimentation rate (ESR), immuneglobulin (Ig), anti-nuclear antibody (ANA), anti-SSA, and anti-SSB. The proportions of B cells in peripheral blood and the levels of serum inerleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and B cell activating factor belonging to the TNF family (BAFF) were measured at baseline and at the end of follow up of 24 weeks. The average score of ESSPRI in both groups had no statistical significance at 24th week. The mean of ESSPRI in the dry-mouth part of questionnaire in patients who scored 3 to 6 points was significantly reduced in the TGP group changed from (4.81 ± 0.60) at baseline to (4.20 ± 1.46) (P = 0.027) at week 24. Stimulated salivary flow rate increased at week 24 from (1.80 ± 0.39) to (2.01 ± 0.51) (P = 0.031) and unstimulated salivary flow rate increased from (0.65 ± 0.46) to (0.78 ± 0.45) (P = 0.011) in the TGP group, but the placebo group showed no significant difference. Erythrocyte sedimentation rate (ESR) was decreased significantly compared to the placebo group at 12- and 24-week from (40.9 ± 18.0) to (29.4 ± 12.2) (P = 0.003) and (30.4 ± 17.3) (P = 0.024). The percentage of naive B cells decreased at week 24 in the TGP group from (77.34 ± 12.20) to (64.59 ± 15.60) (P = 0.005) while memory B cells increased from (21.79 ± 11.97) to (34.21 ± 15.48) (P = 0.006) respectively. The concentrations of TNF-α and IFN-γ decreased in the TGP group at week 24 from (32.51 ± 26.67) to (24.22 ± 13.56) (P = 0.017) and (10.71 ± 8.94) to (6.55 ± 4.88) (P = 0.022), respectively. No significant difference in ANA titer, anti-SSA antibodies, anti-SSB antibodies, C3 concentration or C4 concentration was observed between the two groups. TGP appears to improve the glandular secreting function and decrease the level of inflammatory cytokines.

OBJECTIVE A recent genome-wide association study identified that genetic variants in DPP4 and CCR6 are connected with a risk of RA in the Han Chinese population. The aim of this study was to estimate the epistatic interaction between DPP4 and CCR6 in RA. METHODS Two single-nucleotide polymorphisms identified in a Han Chinese genome-wide association study (rs12617656 in DPP4, rs1854853 in CCR6) were genotyped. Logistic regression was used to estimate the multiplicative interaction and the additive interaction was analysed by 2 × 2 factorial design. RESULTS A total of 1224 subjects (377 RA patients, 847 healthy controls) were included in the initial analysis. Additionally, 600 patients with lupus arthritis were included for comparison. Significant multiplicative interaction between DPP4 and CCR6 was observed in RA [codominant model: odds ratio (OR) = 1.49, P = 0.003]. The epistatic effect seems to be stronger in ACPA-positive RA (codominant model: OR = 1.66, P = 0.001). However, no significant multiplicative interactions were observed in ACPA-negative RA or lupus arthritis. Additive interaction analysis showed a significant epistatic effect, but only in ACPA-positive RA [attributable proportion due to interaction = 0.48 (95% CI 0.10, 0.85)]. A further replication study of an independent cohort (476 subjects) found similar results. Pooled results confirmed that there was significant interaction between DPP4 and CCR6 on both the multiplicative and additive scales. CONCLUSION The study suggests that a genetic interaction between DPP4 and CCR6 is involved in RA susceptibility. Furthermore, these findings highlight Th17 cell response as an important contributor in the pathogenesis of RA.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder characterized by multisystem organ involvement and unclear pathogenesis. Several adipokines synthesized in the adipose tissue, including leptin, adiponectin, resistin, and chemerin, have been explored in autoimmune rheumatic diseases, especially SLE, and results suggest that these mediators may be implicated in the pathogenesis of SLE. However, the current results are controversial. In this review, we will briefly discuss the expression and possible pathogenic role of several important adipokines, including leptin, adiponectin, resistin, and chemerin in SLE.

The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

Systemic lupus erythematosus (SLE) is associated with increased risk of cardiovascular disease. Carotid intima media thickness (CIMT) and carotid plaques are both frequently used to identify populations at higher cardiovascular risk. A systematic literature search and meta-analysis were performed to evaluate CIMT and carotid plaques difference between SLE patients and normal controls.The literatures comparing markers of cardiovascular risk (CIMT and prevalence of carotid plaques) in SLE and controls were systematically searched in PubMed, EMBASE and Cochrane databases. The overall mean CIMT difference and pooled odds ratio (OR) for the prevalence of carotid plaques between SLE patients and control groups were calculated by fixed-effects or random-effect model analysis. Meta-regression was performed to explore the potential influencing factors. Publication bias was examined by a funnel plot and Egger's test.A total of 80 studies (6085 SLE patients and 4794 controls) were included in the final analysis, 71 studies with data on CIMT (4814 cases and 3773 controls) and 44 studies reporting on the prevalence of carotid plaques (4417 cases and 3528 controls). As compared to controls, SLE patients showed a higher CIMT (WMD: 0.07 mm; 95%CI: 0.06, 0.09; P0.001), and an increased prevalence of carotid plaques (OR: 2.45; 95%CI: 2.02, 2.97; P0.001). Meta-regression models showed that traditional cardiovascular risk factors (age, HDL and triglyceride of SLE patients) and lupus related risk factors (as expressed by duration, ESR, SLEDAI and steroids) had a significant influence on CIMT, steroids and triglyceride had significant influence on the prevalence of carotid plaques.Our findings support the current evidence base for an increased cardiovascular burden in SLE patients and support the use of CIMT and carotid plaques in observational studies in SLE patients. The findings are of importance to design more specific prevention and treatment strategies.

This study aims to derive a more precise estimation on carotid intima-media thickness (CIMT) level in patients with rheumatoid arthritis (RA) and related factors. Studies published from January 1, 1982 to December 31, 2014 in English, which comparing CIMT between RA group and control group were searched in PubMed, Embase, and Cochrane Library databases. Heterogeneity test was performed, and publication bias was evaluated. Stata software 12.0 was used to perform the meta-analysis. Two-thousand one hundred sixty-three articles were obtained after searching databases, and 47 studies were finally included in the meta-analysis. The result of the analysis in random effect model showed that RA group had significantly higher CIMT than control group, with the standardized mean difference (SMD) of 1.04 and 95% CI (0.81,1.27). To evaluate the stability of our results, sensitivity analyses were performed, and the results showed no significant change when any one study was excluded. Subgroup analyses showed that region, race, age, BMI, and disease duration were associated with CIMT in RA patients. In summary, CIMT in RA patients is thicker than healthy controls, and it is influenced by region, race, age, BMI, and disease duration.

Objective Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants. Methods Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing. Results More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously. Conclusion Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes.

Currently published data regarding the relationship between plasma/serum leptin levels and systemic lupus erythematosus (SLE) are contradictory. To derive a more precise evaluation of this relationship, a meta-analysis was performed.Published literature from PubMed, Embase and Cochrane Library were obtained. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by fixed-effects or random-effect model analysis. Heterogeneity among studies was estimated using the Cochran Q and I(2) statistics.A total of 11 studies including 868 SLE patients and 591 controls were finally included in the meta-analysis. No significant differences in plasma/serum leptin levels was found between SLE patients and healthy controls when all studies were pooled into the meta-analysis (pooled SMD = 0.269, 95% CI = -0.188 to 0.726). However, subgroup analyses showed that SLE patients from an Asian population, age ≥40 years and BMI25 had higher plasma/serum leptin levels when compared with controls.There is no significant difference in plasma/serum leptin levels between the entire group of SLE patients and controls. However, plasma/serum leptin levels are significantly higher in the subgroup of SLE patients from an Asian population ≥40 years of age and with a BMI25.

Acute gouty arthritis is the inflammation of joint tissues in the acute form due to the deposition of monosodium urate (MSU) crystals. Regulatory T cells (Tregs) and Th17 cells play an important role in the development and progression of inflammatory diseases. However, the expression and role of Tregs and Th17 cells are not clear in this disease. Here, we investigated the changes of Tregs, Th17 cells, and Treg/Th17 ratio in spleen, as well as the inflammatory cytokines in blood and joint tissue pathology in acute gouty arthritis rat induced by MSU. We found that both the percentages of Tregs and Th17 cells in spleen increased at an early stage (6 h). Tregs decreased at 12 and 24 h, and rise again at 48 and 72 h. However, Th17 cells reached its peak at 24 h, and then decreased after 48 h. Treg/Th17 ratio showed an initial decrease and then increase, and further reached its minimum value at 24 h. But the ratios of Treg/Th17at all times were lower than that of normal control. The level of serum cytokines (IL-1β, IL-6, IL-17, TNF-α, and IL-10) showed an opposite trend to Treg/Th17 ratio, except the level of TGF-β1 was similar to Tregs. In summary, Tregs and Th17 cells in spleen changed over time during the development of acute gouty arthritis. Decrease of Treg/Th17 ratio was consistent with inflammation development in the joints, suggesting that Treg/Th17 imbalance may involve in pathogenesis of acute gouty arthritis.

Cardiovascular (CV) risk in type 1 diabetes mellitus (T1DM) is increased. In this study, we evaluated the differences in major markers of CV risk between patients with T1DM and healthy controls by a systematic review and meta-analysis. Literature from PubMed, EMBASE, and The Cochrane Library comparing CV risk markers between patients with T1DM and controls was obtained. The overall standard mean differences (SMDs) of carotid intima–media thickness (cIMT), endothelium-dependent flow-mediated dilation (FMD%), carotid-femoral pulse wave velocity (cf-PWV), and glyceryl trinitrate-mediated dilatation (GTN%) with its 95% confidence interval (CI) between patients with T1DM and control groups were calculated using fixed-effect or random-effect model. Heterogeneity was evaluated using the Cochran Q and I2 statistics. The results showed that patients with T1DM had a significantly greater cIMT (SMD: 0.89; 95% CI, 0.69-1.09; P < .001), significantly lower FMD% (SMD: −1.45%; 95% CI, −1.74 to −1.17; P < .001), significantly increased cf-PWV (SMD: 0.57; 95% CI, 0.03-1.11; P < .001), and significantly decreased GTN% (SMD: −1.11; 95% CI, −1.55 to −0.66; P < .001) than controls. Our results support the current evidence for an elevated CV burden in patients with T1DM and affirm the clinical utility of markers of subclinical atherosclerosis in the management of these patients.

Influence of epidemiology and ethnicity on systemic expression of primary Sjogren syndrome in 9974 patients

Objectives To take a “high-definition” picture of the main features of primary Sjogren syndrome (SjS) following a worldwide data-sharing cooperative merging of international clinical SjS databases. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014 including leading clinical centres in SjS of the 5 continents that shared a harmonised data architecture and conducted cooperative online efforts to refine collected data of primary SjS patients fulfilling the 2002 classification criteria. Results By January 2018, the participant centres had included 10 475 patients from 22 countries, including 7637 (73%) patients from Europe, 1420 (14%) from America, 1186 (11%) from Asia, 167 (1.4%) from Australia and 65 (0.6%) from Africa. The cohort included 9781 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years. The frequencies of fulfilment of the 2002 criteria were 92% for dry eye, 94% for dry mouth, 83% for abnormal ocular tests, 82% for positive minor salivary gland biopsy, 78% for abnormal oral diagnostic tests and 76% for positive anti-Ro/La antibodies. The frequency of positive immunological markers at diagnosis was 79% for ANA, 73% for anti-Ro, 49% for RF, 45% for anti-La, 13% for low C3 levels, 14% for low C4 levels and 7% for cryoglobulins. Conclusions International data sharing-based projects merging disperse clinical registries may be essential tools to increase current knowledge and to improve patient care in specific systemic autoimmune diseases. Disclosure of Interest None declared

To evaluate the efficacy and safety of total glucosides of peony (TGP) in adults with primary Sjögren's syndrome (pSS). A multi-center, randomized, double-blinded, placebo-controlled study was conducted between March 2012 and July 2014 at ten Chinese hospitals. In total, 320 pSS patients-classified according to the 2002 American-European Consensus Group Criteria-were randomized (2:1 ratio) to receive TGP(600 mg, tid) in the TGP group or placebo for 24 weeks in the placebo group. Study personnel, investigators, and patients were blinded to the treatment grouping. The primary endpoint was the improvement of EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at week 24. The secondary endpoints were dry eyes/mouth/skin/nose/throat/vagina visual analogue scale (VAS), pain and discomfort VAS, fatigue VAS, mental discomfort VAS, patient global assessment (PGA), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, basal/stimulated salivary flow-rate values, and erythrocyte sedimentation rate (ESR). All adverse events were recorded during the trial period. ESSPRI improved more in the TGP than the placebo group (p 0.001). Dry eyes/throat/vagina VAS, fatigue VAS, mental discomfort VAS, PGA, Schirmer's test, and ESR also improved more in the TGP group than in the placebo group (all p 0.05). Stimulated salivary flow-rate values increased in the TGP group at week 12 but not at week 24. Adverse events in TGP group were 10.9%. TGP can alleviate some dryness symptoms as well as disease activity in pSS patients over 24 weeks. TGP was well tolerated by study subjects. TGP seems to be an effective and safe treatment for pSS.

Objectives To analyse the influence of geolocation on the clinical systemic presentation of primary Sjogren syndrome (SjS) at diagnosis. Methods The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. Centres were classified by continent, with an additional north-south sub-classification according to latitude (>or or or Results The highest baseline ESSDAI scores were reported from Southern vs Northern countries in Europe (7.2 vs 4.6, p Conclusions This study provides the first evidence for a strong influence of geolocation on the systemic phenotype of primary SjS at diagnosis. Geographical determinants should be considered as key variables when systemic disease is scored. Disclosure of Interest None declared

Pulmonary arterial hypertension (PAH) is an increasingly recognized complication of systemic lupus erythematosus (SLE). This study aims to estimate the point prevalence of PAH and identify risk factors for PAH in a large cohort of hospitalized SLE patients. We have collected the medical records of patients hospitalized with SLE at the First Affiliated Hospital of Anhui Medical University and Anhui Provincial Hospital. Resting transthoracic echocardiography (TTE) was used to estimate pulmonary artery pressure (PAP) and PAH was defined as systolic PAP (PASP) > 30 mmHg. Patients with other connective tissue diseases, aPL syndrome, left heart disease, valvular heart disease, congenital heart disease, HIV, and portal hypertension were excluded because of diseases affecting the PAP. We assessed potential risk factors for PAH such as thrombogenic factors, SLE clinical manifestations, laboratory abnormalities and disease activity. Ninety-five were diagnosed with PAH of 1639 patients with SLE. The presence of high fibrinogen, serositis, and thrombocytopenia were significantly higher in patients with PAH than in those without PAH (all P

Objective Total glucosides of paeony (TGP) have been confirmed to exert anti-inflammatory and hepatoprotective effects. Methotrexate (MTX) and Leflunomide (LEF) combination has a better efficacy in the treatment of active rheumatoid arthritis (RA), but hepatotoxicity was observed. In this study, we investigated the effect of TGP on hepatic dysfunction caused by MTX and LEF in patients with active RA. Methods A total of 268 patients with active RA (disease activity score in 28 joints, DAS28 > 3.2) were enrolled in this study. All patients were randomly assigned to two groups, the therapeutic group in which patients were treated with TGP (1.8 g/day) combined with MTX and LEF (MTX 10 mg/week plus LEF 20 mg/day) while in the control group, patients were treated without TGP up to 12 weeks. The efficacy and liver abnormalities were observed. Results The incidence of abnormal liver function within 12 weeks in TGP group was significantly lower than that in control group (11.38% vs 23.26%, P = 0.013). The proportion of patients with ALT/AST > 3 times ULN (upper limits of normal) was significantly lower in TGP group than control group (1.63% vs 7.75%, P = 0.022). More patients achieved remission, good and moderate response in TGP group than control group at 4, 8 and 12 weeks, but the difference was not significant ( P > 0.05). The proportions of all adverse events were comparable in the two groups except for diarrhea. Conclusions Our study demonstrates that TGP can significantly reduce the incidence and severity of liver damage caused by MTX + LEF in the treatment of active RA patients.

Long noncoding RNA (lncRNA), with size larger than 200 nucleotides, is a new class of noncoding RNA. Emerging evidence has revealed that lncRNAs play a key role in the regulation of immunological functions and autoimmunity. Herein, we review the recent findings of lncRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. In addition, we focus on the involvement of lncRNA regulation in innate and adaptive immune responses, immune cell development, and differential expression of lncRNAs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), multiple sclerosis (MS), autoimmune thyroid disease (AITD), psoriasis, polymyositis/dermatomyositis (PM/DM) and Crohn's disease (CD).

Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility.The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction.Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets.Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.

The objective of this study is to evaluate the remission rate and describe the current use of medication in a large cohort of rheumatoid arthritis (RA) patients under routine clinical care in China. RA patients were recruited from 40 large teaching hospitals nationwide in China. Data regarding RA disease activity, medication treatment, and adverse events were recorded using a standardized clinical data questionnaire. RA remission was evaluated by the 28 Joint Disease Activity Score DAS28-ESR Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria. A total of 1945 patients with RA were included in the study. The proportions of patients who fulfilled the DAS28-ESR, CDAI, SDAI, and ACR/EULAR remission criteria were 10.90%, 6.17%, 5.04% , and 1.75%, respectively. Most patients had taken at least one disease-modifying anti-rheumatic drug (DMARD), and the most common prescriptions included leflunomide (LEF) and methotrexate (MTX). DMARD combined with botanics were the most common and dominant strategy for RA management (29.16%). Overall, 433 patients (22.27%) had at least one adverse event. Gastrointestinal adverse events (41.27%) were the most frequently reported events. The incidence of side effects in patients using biologics DMARDs (bDMARDs) was significantly lower than that in those taking MTX, LEF, or sulfasalazine (SSZ). The remission rate of RA disease activity, as assessed in Chinese clinical practice, was very low. Adverse effects of the medicine occurred in approximately one in five RA patients, with bDMARDs were demonstrated to be the medication with the lowest side effects.

Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjogren Syndrome : Characterization Of Systemic Disease

Objectives Baseline characterization of European patients diagnosed with primary Sjogren syndrome (SS) according to the 2002 AE criteria. Methods The Big Data Sjogren Project was formed in 2014 to take a “high-definition” picture of the main features of primary SS by merging international SS databases. International experts of the EULAR-SS Task Force were invited to participate. By January 2017, the database included 9302 consecutive patients recruited from 21 countries of the 5 continents. Results A total of 6586 (71%) patients were included from European countries. In comparison with non-European countries, European patients had a higher mean age (54 v 51yrs, p Conclusions European patients are diagnosed at older age, are more frequently men, and presented a lower frequency of anti-Ro/La antibodies and a higher frequency of immunological markers related to mixed cryoglobulinemia. Disclosure of Interest None declared

Introduction: Hypoxia-inducible factor-1α (HIF-1α) plays a crucial role in both innate and adaptive immunity. Emerging evidence indicates that HIF-1α is associated with the inflammation and pathologic activities of autoimmune diseases.Areas covered: Considering that the types of autoimmune diseases are complicated and various, this review aims to cover the typical kinds of autoimmune diseases, discuss the molecular mechanisms, biological functions and expression of HIF-1α in these diseases, and further explore its therapeutic potential.Expert opinion: Inflammation and hypoxia are interdependent. HIF-1α as a key regulator of hypoxia, exerts a crucial role in the balance between Th17 and Treg, and involves in the inflammation and pathologic activities of autoimmune diseases. Although there are many challenges remaining to be overcome, targeting HIF-1α could be a promising strategy for autoimmune diseases therapies.

Elevated serum IgG4 levels are an important hallmark for diagnosing IgG4-related disease (IgG4-RD) but can also be found and reported in other diseases. The present study intended to compare the serum IgG4 levels in both IgG4-RD and non-IgG4-RD and determine the serum IgG4 levels in patients with IgG4-RD before and after glucocorticoid therapy.The study included 323 patients from Anhui Medical University Affiliated Provincial Hospital (China) and was conducted from July 2014-January 2016. A total of 25 patients were eventually diagnosed as having IgG4-RD, according to the IgG4-RD diagnostic criteria. Our study also included 108 patients with connective tissue disease, 94 patients with pancreatic lesions, 66 patients with bile duct lesions, 13 patients with carcinoma of the duodenal papilla and 20 control participants. The assay for serum IgG4 detection was peformed using the nephelometric method.Elevated levels of serum IgG4 (1.35g/L) were detected in all patients with IgG4-RD, and reduced levels of serum IgG4 (1.35g/L) were found in all patients with non-IgG4-RD. The serum IgG4 level in patients with IgG4-RD after glucocorticoid therapy was significantly lower than that before glucocorticoid therapy (t = 2.426, P = 0.04).High levels of IgG4 were observed in IgG4-RD. However, a diagnosis of IgG4 disease can not only be dependent on the detection of elevated serum IgG4 levels but also may need clinical manifestations, serology, histopathology and other comprehensive information for verification.

AIM The aim of this study was to estimate the influence of socioeconomic and geographical variables on disease phenotype and activity of systemic lupus erythematosus (SLE) in a Chinese population. METHODS Data on 904 therapy-naive SLE patients from the Chinese SLE Treatment and Research Group (CSTAR), which is a nation-wide database of SLE patients, were used to evaluate the influence of socioeconomic status (SES) and geographical regions on disease phenotypes. The influence of regional climate and economic variables (i.e., data from the database of the Chinese Statistical Yearly Annals) on disease activity and nephropathy was further analyzed in a multivariate analysis to identify some of the environmental factors contributing to SLE. RESULTS Phenotype differences in SLE were found between patients with different SES. In the multivariate regression analysis that considered regional economic and climate factors, after adjusting for age, gender and disease duration, lower educational levels (β: -0.122, P = 0.001), lower availability of medical technical personnel (MTP) per 1000 people (β: -0.192, P < 0.001), higher annual duration of sunshine (β: 0.178, P = 0.010) and residence in southern China (β: 0.165, P = 0.001) were significantly associated with higher disease activity scores. Living in southern China (odds ratio [OR]: 1.907, P = 0.002) seemed to be a significant risk factor for nephropathy. A high number of MTP per 1000 people (OR: 0.951, P = 0.014) and relatively high temperatures were determined to be protective factors for nephropathy (OR: 0.946, P = 0.011). CONCLUSIONS The phenotype pattern and disease activity varied between SLE patients by SES and other regional variables, such as educational level, availability of medical technical personnel, annual sunshine duration and regional temperature.

AIM Our previous study confirmed the defect of B7-H4 expression in peripheral blood and salivary glands of patients with primary Sjogren's syndrome (pSS). The aim of this study was to analyze the effect of the deficit expression of B7-H4 on CD4+ T cells. METHODS CD4+ T cells were purified by magnetic-activated cell sorting MACS. The proliferation and cytokine production of CD4+ T cells co-cultured with purified salivary gland epithelial cells (SGECs) from pSS or non-SS sicca syndrome were detected. RESULTS By co-culturing the gland cells with CD4+ T cells, we found the proliferation of CD4+ T cells was significantly suppressed. The effect was weaker when SGECs from pSS patients were used compared to that from non-pSS sicca syndrome controls. Simultaneously, the productions of cytokines interleukin (IL)-5, IL-13, IL-17A, IL-6 in supernatant were reduced and also SGECs from pSS patients decreased them less than that from non-SS controls. CONCLUSIONS The decrease of B7-H4 expression in salivary glands of SS patients contributes to the defect of negatively regulating the inflammation caused by CD4+ T cells, thereby providing new insights into the role of B7-H4 in the inflammatory process of salivary glands in SS.

Aim Febuxostat, a novel non-purine selective inhibitor of xanthine oxidase, has been identified as a potential alternative to allopurinol in patients with hyperuricemia. The purpose of this study was to compare the urate-lowering (UL) efficacy and safety of daily febuxostat and allopurinol in Chinese gout patients with hyperuricemia. Methods Gout patients (n = 512) with serum uric acid (sUA) concentrations of at least 8.0 mg/dL were randomized to receive daily febuxostat 40 mg or 80 mg or allopurinol 300 mg for 28 weeks. Prophylaxis against gout flares with meloxicam or colchicine was provided during weeks 1 through 8. The primary endpoint was the percentage of subjects achieving a sUA concentration of

Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases. Therefore, therapeutic modulation of Tregs could be a potent means of treating autoimmune diseases. Human Tregs are diverse, however, and not all of them have immunosuppressive effects. Forkhead box P3 (Foxp3), a pivotal transcription factor of Tregs that is crucial in maintaining Treg immunosuppressive function, can be expressed heterogeneously or unstably across Treg subpopulations. Insights into modulating Treg differentiation on the level of DNA transcription or protein modification may improve the success of Treg modifying immunotherapies. In this review, we will summarize three main prospects: the regulatory mechanism of Foxp3, the influence on Foxp3 and Tregs in autoimmune diseases, then finally, how Tregs can be used to treat autoimmune diseases.