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Hypoxia-inducible factor-1α (HIF-1α) is a primary metabolic sensor, and is expressed in different immune cells, such as macrophage, dendritic cell, neutrophil, T cell, and non-immune cells, for instance, synovial fibroblast, and islet β cell. HIF-1α signaling regulates cellular metabolism, triggering the release of inflammatory cytokines and inflammatory cells proliferation. It is known that microenvironment hypoxia, vascular proliferation, and impaired immunological balance are present in autoimmune diseases. To date, HIF-1α is recognized to be overexpressed in several inflammatory autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and function of HIF-1α is dysregulated in these diseases. In this review, we narrate the signaling pathway of HIF-1α and the possible immunopathological roles of HIF-1α in autoimmune diseases. The collected information will provide a theoretical basis for the familiarization and development of new clinical trials and treatment based on HIF-1α and inflammatory autoimmune disorders in the future.

Objective: Systemic lupus erythematosus is a chronic rheumatic disorder. Endothelin-1, a vasoconstrictor, belongs to the endothelin family. To date, association between ET-1 and pathogenesis of SLE remains unclear. Method: This case-control study was carried out by 314 SLE, 252 other inflammatory autoimmune diseases patients and 500 healthy controls. Serum ET-1, CCN3, IL-28B levels were detected by ELISA, and ET-1 gene polymorphisms (rs5369, rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs4145451, rs6458155, rs9369217) were genotyped with KASP. Results: Raised ET-1 concentrations in SLE patients correlated with clinical characteristics. Serum CCN3, IL-28B expressions were higher in SLE patients, and ET-1 levels were positively correlated with the two cytokines. Rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs6458155 and rs2070699 were associated with SLE risk. Rs2070699 (T, TT) was related to alopecia. Rs5370 (T, TT, TG), rs1476046 (G,GA), rs2071942 (G,GA) and rs2071943 (G,GA) were associated with pericarditis, pyuria and fever manifestations. Rs3087459 (CC) and rs9369217 (TC) were relevant to anti-SSB indicator. Rs5369 (AA) was associated with IgG and CRP levels. Conclusion: elevated serum ET-1 in SLE patients may be a potential disease marker, and its gene polymorphisms were relevant to SLE susceptibility.

Additional file 2. QoR-15 score.

Additional file 1. Preoperative, intraoperative and postoperative CRFs.

Tenofovir (TDF) and entecavir (ETV) are first-line treatments for patients with chronic hepatitis B virus (HBV) infection. However, the effect of TDF versus ETV on the prognosis of HBV-related hepatocellular carcinoma (HCC) has not been fully clarified yet. PubMed, Embase and Web of science were searched up to March, 2021. Meta-analyses were performed for overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) to assess the effect of TDF versus ETV on the prognosis of HBV-related HCC. A total of 10 studies comprising 4706 Asian patients were included. The pooled results revealed that TDF was associated with better OS (adjusted HR = 0.50, 95% CI: 0.40–0.62; I2 = 36.0%, p = 0.167) and better RFS/DFS (adjusted HR = 0.70, 95% CI: 0.55–0.89, I2 = 71.9%, p = 0.002) than ETV in treatment of HBV-related HCC. Subgroup analysis revealed that OS benefit from TDF was generally consistent, except for patients who underwent non-surgical treatment for HCC. Subgroup analysis also indicated that TDF reduces the risk of late recurrence (HR = 0.41, 95% CI: 0.18–0.0.93; I2 = 63.0%, p = 0.067) rather than early recurrence (HR = 0.99, 95% CI: 0.64–1.52; I2 = 61.3%, p = 0.076). Compared with ETV, TDF has the advantage of improving OS and reducing late recurrence of patients with HBV-related HCC patients who underwent resection.

Additional file 3. Informed consent form.

Enhancer of zeste homolog 2 (EZH2) is a histone methylated enzyme. It trimethylates histone 3 lysine 27 (H3K27) to regulate epigenetic processes. Recently, studies showed excessive expression of EZH2 in rheumatic diseases, such as systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, and systemic sclerosis. Moreover, epigenetic modification of EZH2 regulates differentiation and proliferation of different immune cells. Therefore, in this review, we comprehensively discuss the role of EZH2 in rheumatic diseases. Collection of the evidence may provide a basis for further understanding the role of EZH2 and give potential for targeting these diseases.

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.

The relationship between rheumatoid arthritis (RA) and the risk of leukemia was still controversial. This study aimed to assess the risk of leukemia in patients with rheumatoid arthritis by systematic review and meta-analysis.Relevant studies were identified by searching PubMed, Embase, Cochrane Library, and SinoMed up to December 2019. Random effects model analysis was used to pool standardized incidence ratios (SIRs) and 95% confidence interval.A total of 15 relevant studies that met the criteria were included. Compared with the general population, patients with RA showed an increased risk of leukemia (SIR = 1.51, 95% CI: 1.34-1.70). The statistical heterogeneity was moderate with an IOur findings suggested that the risk of leukemia in RA was increased compared with the general population. Key points • This is the first systematic review and meta-analysis to assess the risk of leukemia in RA. • Our study suggested that the risk of leukemia in RA was increased compared with the general population. • This study indicated that the risk of leukemia in RA was higher in non-Asian populations.

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.

TL1A, also called TNFSF15, is a member of tumor necrosis factor family. It is expressed in different immune cell, such as monocyte, macrophage, dendritic cell, T cell and non-immune cell, for example, synovial fibroblast, endothelial cell. TL1A competitively binds to death receptor 3 or decoy receptor 3, providing stimulatory signal for downstream signaling pathways, and then regulates proliferation, activation, apoptosis of and cytokine, chemokine production in effector cells. Recent findings showed that TL1A was abnormally expressed in autoimmune diseases, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, primary biliary cirrhosis, systemic lupus erythematosus and ankylosing spondylitis. In vivo and in vitro studies further demonstrated that TL1A was involved in development and pathogenesis of these diseases. In this study, we comprehensively discussed the complex immunological function of TL1A and focused on recent findings of the pleiotropic activity conducted by TL1A in inflammatory autoimmune disease. Finish of the study will provide new ideas for developing therapeutic strategies for these diseases by targeting TL1A.

Previous studies have shown that silent information regulator 1 (SIRT1) expression is elevated in rheumatoid arthritis (RA) patients. However, whether gene polymorphisms in SIRT1 gene associated with RA in a Chinese Han population remains to be discussed.In this case-control study, 529 RA patients and 700 healthy controls were selected, and association of 11 SIRT1 gene polymorphisms (rs12415800, rs3740051, rs932658, rs3740053, rs7895833, rs10509291, rs33957861, rs7069102, rs2273773, rs3818292, rs1467568) with RA susceptibility was evaluated.Frequency of GA+GG genotype of rs3740051 in RA patients was significantly lower than that in healthy controls (P = .037). Frequencies of GC and GC+GG genotypes of rs7069102 were significantly lower than those in healthy controls (P = .036, P = .047). Frequencies of GA and GA+GG genotypes of rs1467568 were lower in RA patients as compared to those in healthy controls (P = .011, P = .013). For rs2273773, RA patients who carried the T allele had higher number of tender joints than patients who carried the C allele (P = .033). Other polymorphisms did not associate with RA risk.The findings suggest that rs3740051, rs7069102 and rs1467568 variants in SIRT1 gene are related to RA susceptibility in a Chinese Han population.

Interleukin‐29 (IL‐29) is a newly discovered member of type III interferon. It mediates signal transduction via binding to its receptor complex and activates downstream signalling pathways, and therefore induces the generation of inflammatory components. Recent studies reported that expression of IL‐29 is dysregulated in inflammatory autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, Sjögren's syndrome, psoriasis and systemic sclerosis. Furthermore, functional analysis revealed that IL‐29 may involve in the pathogenesis of the inflammatory autoimmune disorders. In this review, we will systematically review the current knowledge about IL‐29. The information collected revealed the regulatory role of IL‐29 and may give important implications for its potential in clinical treatment.

This study evaluated expression of circRNA in primary Sjögren's syndrome (pSS) patients so as to find novel biomarkers for pSS screening and discussed possible role of circRNA in pSS. We also evaluated expression profile of circRNA in systemic lupus erythematosus (SLE) patients.Microarray analysis detected circRNA expression in PBMCs from five paired pSS, SLE patients, and controls. Then, differentially expressed circRNAs were validated in 30 pSS patients as compared to 30 SLE patients, healthy controls. CircRNAs interacting with miRNAs were discussed by Arraystar's homemade miRNA target prediction software. ROC analysis assessed the diagnostic value.We identified 234 differentially expressed circRNAs in pSS patients and verified five selected circRNAs (including hsa_circRNA_001264, hsa_circRNA_104121, hsa_circRNA_045355, hsa_circRNA_103461, hsa_circRNA_105034). Expression of hsa_circRNA_001264, hsa_circRNA_104121, and hsa_circRNA_045355 was strongly related to some clinical, laboratory parameters, and disease activity index in pSS patients. ROC analysis indicated potential diagnostic ability for the three circRNAs in pSS patients. One hundred and forty-eight circRNAs were differently expressed between lupus patients and controls.This study provides evidence that hsa_circRNA_001264, hsa_circRNA_104121, and hsa_circRNA_045355 might be biomarkers for pSS, correlate with pSS etiology.Key Points• Many circRNAs were dysregulated in pSS patients.• Differentially expressed circRNAs correlated with pSS clinical, laboratory features.• CircRNAs may be biomarkers for pSS.

Interleukin-34 (IL-34) shares a common receptor with macrophage colony-stimulating factor (M-CSF), and can bind to CSF-1R, induces lymphocytes differentiation, proliferation, and regulates the synthesis of inflammatory components. Recent findings reported aberrant expression of IL-34 in several autoimmune disorders, such as lupus, arthritis, systemic sclerosis, inflammatory bowel diseases. The functional analysis further demonstrated that IL-34 may perform significantly in these inflammatory autoimmune disorders. IL-34 might consider as a biomarker for these diseases. I hope this collection of the findings in this review will improve knowledge of the role of IL-34, and targeting IL-34 may give the potential for these autoimmune diseases.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with local, systemic inflammation, such as persistent synovial inflammation. Interaction of immune cells and inflammatory mediators results in amplification and perpetuation of inflammatory, remodelling process. This disease is characterized by joints swelling, redness, and arthralgia.

Despite the high incidence and mortality of cardiovascular events in hyperuricemia patients, the role of serum uric acid in cardiovascular diseases is still controversial. The aim of this meta-analysis was to explore the difference of carotid intima-media thickness in hyperuricemia and control groups. We performed this meta-analysis by searching the PubMed, Cochrane Library, Embase and Web of Science databases up to July 2020. The 95% confidence intervals and standard mean differences were calculated to analyze the differences in carotid intima-media thickness in hyperuricemia groups and control groups. Sensitivity analysis, subgroup analysis and meta-regression were used to explore the sources of heterogeneity. Publication bias was evaluated by funnel plot and Begg’s regression test. We used Stata 14.0 software to complete our analyses. A total of 8 articles were included. The results showed that there was a significant increase in carotid intima-media thickness in the hyperuricemia groups compared with the control groups [SMD = 0.264, 95% CI (0.161–0.366), 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.

Interleukin (IL)-35 is the newest member of the IL-12 family. It is expressed in many immune cells and has been recognized as a novel inflammatory cytokine that may have bifunctional properties. Recent findings have indicated that the expression of IL-35 is abnormal in rheumatoid arthritis (RA) patients. However, the results were inconsistent. In this study, 400 RA patients were recruited to evaluate serum levels of IL-35 in a Chinese Han population by enzyme-linked immunosorbent assay. The association of IL-35 gene polymorphisms and RA genetic susceptibility was investigated in 400 RA patients and 612 healthy controls. The results showed that serum levels of IL-35 were elevated in 100 RA patients compared to 51 healthy controls, relating to disease activity and synovial fluid IL-35 expression in the training cohort. Another independent 300 RA patients and 369 other rheumatic disease patients (98 lupus, 95 osteoarthritis, 95 gout, 42 Sjogren's syndrome and 39 ankylosing spondylitis patients) confirmed that serum levels of IL-35 were elevated in RA patients, and serum IL-35 has good diagnostic ability for differentiating RA from the other rheumatic diseases. The genotyping of 10 IL-35 polymorphisms, including rs2227314, rs2243115, rs2243123, rs2243131, rs568408, rs583911, rs428253, rs4740, rs9807813 and rs4905, revealed that rs2227314, rs2243131, rs9807813, and rs583911 were correlated with RA risk. Different genotypes (rs2227314, rs583911, and rs9807813) exhibited different expression of IL-35. These findings demonstrate that serum levels of IL-35 are increased in RA patients and that IL-35 polymorphisms are correlated with RA risk.

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 Dysfunction of kidney correlates with multiple renal diseases, for instance, chronic kidney disease. However, monitoring the changes of indexes related to renal function may help to early find the potential patients with renal diseases. Methods A cohort of 14,716 participants (8,148 males and 6,568 females) was recruited from the Health Examination Center at West China Hospital, Sichuan University, and was followed up since 2012 to 2018. Four indexes related to renal function, including creatinine (Cr), uric acid (UA), cystatin C (CysC) and urea nitrogen (UN) were selected to monitor the kidney function. Results Levels of CysC, Cr were reduced, and expression of UA was increased in all the participants since 2012 to 2018 overall. In addition, levels of CysC, UA, Cr and UN were higher in males than those in females, and expression of the four indexes was up-regulated in the elderly population compared with those in the younger population since 2012 to 2018 overall. Conclusions The findings suggested that some preventive action may be adopted early and more attention can focus on the health-examination population.

Interleukin 35 (IL-35) is the recently identified member of the IL-12 family of cytokines and provides the possibility to be a target for new therapies for autoimmune, inflammatory diseases. It is composed of an α chain (p35) and a β chain (EBI3). IL-35 mediates signaling by binding to its receptors, activates subsequent signaling pathways, and therefore, regulates the differentiation, function of T, B cells, macrophages, dendritic cells. Recent findings have shown abnormal expression of IL-35 in inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes, psoriasis, multiple sclerosis, autoimmune hepatitis, experimental autoimmune uveitis. In addition, functional analysis suggested that IL-35 is critical in the onset and development of these diseases. Therefore, the present study will systematically review what had been occurred regarding IL-35 in inflammatory autoimmune disease. The information collected will help to understand the biologic role of IL-35 in immune cells, and give information about the therapeutic potential of IL-35 in these diseases.

Aim This study aims to discuss risk factors associated with cervical spine involvement (CSI) in patients with rheumatoid arthritis (RA). Methods A literature search was performed in Medline, EMBASE, Web of Science and CBMdisc databases for potential studies published before October 2016. The clinical and laboratory data were extracted, and a meta-analysis was performed to evaluate the risk factors for CSI in RA patients. Results Twelve studies involving a total of 2750 cases with RA and 733 CSI (26.65%) were eligible and included in this meta-analysis. The results showed that risk factors for CSI were female (odds ratio [OR] = 1.37, 95% confidence interval [CI]: 1.079–1.74), positive rheumatoid factor (RF) (OR = 1.351, 95% CI: 1.084–1.683), long-term corticosteroids treatment (OR = 2.208, 95% CI: 1.732–2.815), erosion in hands or feet (OR = 2.559, 95% CI: 1.985–3.299), age (weighted mean difference [WMD] = −2.464 years, 95% CI: −3.688 to −1.240), RA duration (WMD = 1.495 years, 95% CI: 0.870–2.121), erythrocyte sedimentation rate (ESR) level (standard mean difference [SMD] = 0.288, 95% CI: 0.161–0.41), C-reactive protein (CRP) level (SMD = 0.288, 95% CI: 0.161–0.415), Disease Activity Score of 28 joints (SMD = 0.5, 95% CI: 0.303–0.697). Conclusion The significant risk factors for CSI in RA were female gender, positive RF, long-term corticosteroids treatment, peripheral joints erosions, younger age, long RA duration, markers of higher disease activity (ESR, CRP and Disease Activity Score).

Innate immune signaling plays an important role in inflammation, and dysregulation of signaling components within this pathway has been focused as a critical mediator in initiation, progression of inflammatory autoimmune diseases. Toll-like receptors (TLRs) are the most upstream pattern recognition receptors in the immune cells, detecting pathogen associated molecular patterns, initiating signal transduction, by which interleukin-1 receptor-associated kinase (IRAK) family mediates activating signal from TLRs and interleukin-1 receptor. The family comprises of four members, IRAK1, IRAK2, IRAK-M, IRAK4. The family members have a role in either positive or negative regulation of innate immunity, adaptive immunity and inflammation. Accumulated evidence proves that IRAK performs significantly in the pathogenesis of inflammatory autoimmune disorders. On the one hand, both patients and animal modes reported abnormal expression of the family members. On the other hand, functional study in vivo and in vitro demonstrated that the members are implicated in the development of the diseases. Interestingly, IRAK inhibition has potential therapeutic benefits. In this review, we focus on the family, review the physiological roles in different immune cells, and summarize emerging data for highlighting the importance of them in inflammatory autoimmunity.

Galectin family is a group of glycan-binding proteins. Members in this family are expressed in different tissues, immune or non-immune cells. These molecules are important regulators in innate and adaptive immune response, performing significantly in a broad range of cellular and pathophysiological functions, such as cell proliferation, adhesion, migration, and invasion. Findings have shown that expression of galectins is abnormal in many inflammatory autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, sjögren's syndrome, systemic sclerosis. Galectins also function as intracellular and extracellular disease regulators mainly through the binding of their carbohydrate recognition domain to glycoconjugates. Here, we review the state-of-the-art of the role that different galectin family members play in immune cells, contributing to the complex inflammatory diseases. Hopefully collection of the information will provide a preliminary theoretical basis for the exploration of new targets for treatment of the disorders.

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.

Systemic lupus erythematosis (SLE) is an inflammatory autoimmune disease with multiple organs, systems damage. To date, the clear pathogenesis of SLE has not been fully clarified. However, genetics, environmental factors and dysregulated immunity were related to onset of this complex disease.

Osteoarthritis (OA) is a chronic degenerative joint disease, characterized by destruction of articular cartilage. This disease can markedly reduce quality of life of OA patients, leading to increased physical and psychological damage, for instance, pain and disability, and causing a serious impact on social economy.

Angiogenesis is defined as the growth of new capillaries sprouting from pre-existing vasculature. Pathological angiogenesis signals can lead to dysregulated development of new vessels. Inflammation is accompanied by pathological angiogenesis. During an inflammatory process, newly formed blood vessels provide oxygen and nutrients to the inflamed tissue, facilitating the transport of inflammatory cells. Therefore, angiogenesis is closely related to pathogenesis of inflammatory autoimmune diseases. As a member of the angiopoietin family, Angiopoietin-2 (Ang-2) plays an irreplaceable role in angiogenesis. This review will narrate the expression of Ang-2 and its role in inflammatory autoimmune diseases. Collecting this information may improve the acquaintance of Ang-2 and provide a theoretical foundation for clinical trials and drug development in the future.

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

AIM This study aims to discuss plasma and messenger RNA (mRNA) levels of interleukin (IL)-37 in rheumatoid arthritis (RA) patients and evaluate the potential of plasma IL-37 as a biomarker for RA. METHOD Plasma IL-37 levels and IL-37 mRNA relative concentrations were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). We discussed the association of IL-37 levels and clinical, laboratory parameters in RA patients in a training cohort. Plasma IL-37 levels were tested for discriminatory capacity by receiver operating characteristic (ROC) curve analysis. We then validated plasma IL-37 expression in a cohort of 598 patients (230 RA, 107 systemic lupus erythematosus [SLE], 100 osteoarthritis [OA], 62 gout, 51 primary Sjogren's syndrome [pSS], 48 ankylosing spondylitis [AS]). RESULTS Both plasma levels of IL-37 and mRNA levels of IL-37 were elevated in RA patients compared to those in healthy controls in the training cohort, and there was a good diagnostic ability to predict RA (area under the curve [AUC] = 0.97). Plasma IL-37 levels were significantly related to Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) (rs = 0.459, P

Previous studies have indicated that interleukin-38 (IL-38) is involved in rheumatoid arthritis (RA). The present study aims to assess plasma levels of IL-38 in RA and discuss the potential of IL-38 as a biomarker for RA. Protein concentrations of IL-38 were examined by enzyme-linked immunosorbent assay, and the mRNA level of IL-38 was tested by quantitative real-time polymerase chain reaction. Plasma IL-38 was first compared in a training cohort, including 130 RA patients and 53 healthy controls, given the optimal cutoff. Then, we validated the levels of IL-38 in a further cohort of 519 patients, including 250 with RA, 63 systemic lupus erythematosus, 62 primary Sjogren's syndrome, 51 gout, 63 osteoarthritis, and 30 psoriatic arthritis, as well as 60 healthy controls. To further discuss the changes in IL-38 after treatment and the relationship with disease activity, we tested IL-38 expression in RA patients from the training cohort under follow-up. In the training cohort, plasma levels of IL-38 were higher in RA patients compared with healthy controls (681.00 [234.45-826.47] versus 152.04 [70.06-246.80] pg/mL, P < 0.001). The IL-38 mRNA level was elevated in RA patients as compared with healthy controls (P < 0.001). Expression of IL-38 was significantly higher in RA patients compared with that in non-RA patients in the validation cohort (all P < 0.001). Treatment significantly reduced IL-38 expression. IL-38 expression was related to parameters of inflammation both at baseline and in the follow-up studies. The area under the curve (AUC) of the receiver-operating characteristic curve showed that IL-38 may be a potential biomarker for RA. At the optimal cutoff value of 341.90 pg/mL, the sensitivity, specificity, and AUC were 72.30%, 90.60%, and 0.840, respectively, in the training cohort. Similar results were noted in the validation cohort. In conclusion, IL-38 expression correlated with RA disease activity, and plasma IL-38 might be a promising diagnostic biomarker for RA.

Autoimmune diseases are characterized by the impaired function and the destruction of tissues that are caused by an immune response in which aberrant antibodies are generated and attack the body's own cells and tissues. Interleukin (IL) -37, a new member of the IL-1 family, broadly reduces innate inflammation as well as acquired immune responses. Recently, studies have shown that expression of IL-37 was abnormal in autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), ankylosing spondylitis (AS), psoriasis, Graves' disease (GD). In addition, functional analysis indicated that IL-37 is negatively involved in the development and pathogenesis of these autoimmune disorders. The strong association of this cytokine with autoimmune diseases promotes us to systematically review what had been published recently on the crucial nature of IL-37 in relation to autoimmune diseases gaining attention for its regulatory capability in these autoimmune disorders.

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 and Aims Studies investigating the association between the peptidylarginine deiminase 4 (PADI4) gene polymorphisms and rheumatoid arthritis (RA) reported conflicting results. The aim of this meta-analysis was to assess the association between PADI4 gene polymorphisms and RA. Methods A systematic literature search was conducted to identify relevant studies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Results A total of 34 studies from 28 articles involving 19859 patients with RA and 25771 healthy controls were included. Significant association of PADI4–94G/A polymorphism and RA was observed (OR = 0.891, 95% CI = 0.833–0.954, p = 0.001) in the overall study population and in the Asian populations (OR = 0.824, 95% CI = 0.759–0.894, p = 0.000) respectively. For the –92C/G polymorphism, a significant association was observed (OR = 1.481, 95% CI = 1.166–1.882, p = 0.001) in Africans. For the –90C/T polymorphism, a significant association was observed (OR = 0.576, 95% CI = 0.381–0.872, p = 0.009) in the Latin American population. The pooled estimates for the other polymorphisms were not statistically significantly associated with RA (PADI4–104C/T, –89A/G, –96T/C). Conclusions This meta-analysis demonstrates that PADI4–94G/A polymorphism is associated with susceptibility to RA in the overall population and in the Asian population. The PADI4 –92C/G polymorphism confers susceptibility to RA in Africans and the PADI4–90C/T polymorphism was associated with RA in the Latin American population.