Involvement of N6-methyladenosine modifications of long noncoding RNAs in systemic lupus erythematosus.

BACKGROUND: LncRNAs are potential biomarkers for SLE, but the epigenetic regulatory mechanisms of N6-methyladenosine (m6A) modification in SLE remain largely unclear. METHODS: In this study, we established m6A modification profile and investigated the potential roles of m6A-related lncRNAs in SLE. The m6A modification profile of SLE was established using MeRIP-seq. Four potential m6A related-lncRNAs (linc02446, linc01410, Xist, and PSMB8-AS1) were selected for validation using qRT-PCR, and their expression and association with clinical characteristics with SLE were evaluated. RESULTS: Overall, m6A level was lower in patients with SLE than in controls. Compared with controls, the expression of the two m6A related-lncRNAs (Xist and PSMB8-AS1) was downregulated in patients with SLE (all P < 0.05); the linc02446 was up-regulated in PBMCs of patients with SLE (Z=-2.738, P = 0.006), while it was not differentially expressed in T cells (Z=-0.387, P = 0.699). No significant alteration in linc01410 expression was observed in patients (Z=-0.940, P = 0.347). The lower expression levels of Xist and PSMB8-AS1 were associated with many clinical manifestations in patients with SLE (all P < 0.05). Additionally, mRNAs co-expressed with m6A related-lncRNAs (Xist, linc02446, and PSMB8-AS1) also participated in SLE. CONCLUSION: These results suggest that m6A methylation and m6A related-lncRNAs might be involved in the pathogenesis of SLE. Thus, our findings provide some clues on the potential function of lncRNAs that m6A modification may target in novel therapeutic or diagnostic strategies for SLE.

Association between ambient air pollution and multiple sclerosis: a systemic review and meta-analysis.

Recently, increasing attention has been paid to the effects of air pollutants on autoimmune diseases. The results of relationship between ambient air pollution and multiple sclerosis (MS) showed a variety of differences. Thus, the purpose of this study is to further clarify and quantify the relationship between ambient air pollutants and MS through meta-analysis. Through electronic literature search, literature related to our research topic was collected in Cochrane Library, Embase, and PubMed till August 18, 2020, according to certain criteria. Pooled risk estimate and 95% confidence intervals (95%CI) were calculated by random-effect model analysis. After removing copies, browsing titles and abstracts, and reading full text, 6 studies were finally included. The results showed that only particulate matter (PM) with aerodynamic diameter ≤ 10 (PM10) was related to MS (pooled HR = 1.058, 95% CI = 1.050-1.066), and no correlation was found between PM with aerodynamic diameter < 2.5 (PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), benzene (C6H6), major road < 50 m, and MS. There was no publication bias, and the heterogeneity analysis results were stable. PM10 is correlated with the disease MS, while other pollution is not connected with MS. Therefore, it is important for MS patients to take personal protection against particulate pollution and avoid exposure to higher levels of PM.

Elevated Urinary and Blood Vascular Cell Adhesion Molecule-1 as Potential Biomarkers for Active Systemic Lupus Erythematosus: A Meta-analysis.

OBJECTIVE: Due to the inconsistent results of current studies on the association between urinary and blood vascular cell adhesion molecule-1 (VCAM-1) and systemic lupus erythematosus (SLE) disease activity, we conducted this study and analyzed its influencing factors. METHODS: A literature search was conducted in PubMed, EMBASE, Web of Science, and Cochrane Library. Data were extracted from eligible studies to calculate standardized mean differences (SMD) with 95% confidence intervals (CI). Cochrane Q test and I2 statistics were used to examine heterogeneity. The sources of heterogeneity were assessed through sensitivity analysis and subgroup analysis. Publication bias was evaluated by funnel plots and Egger's test. RESULTS: A total of 15 studies met the inclusion criteria, including 473 active SLE patients and 674 inactive SLE patients. The random effects model was used for data analysis. In both urine and blood samples, VCAM- 1 level in active SLE patients was significantly higher than those in inactive SLE patients (urine: SMD: 0.769; 95% CI: 0.260-1.278; blood: SMD=0.655, 95% CI: 0.084-1.226). No publication bias was found in this study. CONCLUSION: Compared with inactive SLE patients, patients with active SLE have higher levels of VCAM-1 in both urine and blood. VCAM-1 may be a potential indicator of SLE disease activity.

Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis.

OBJECTIVE: Clinical diagnosis of SLE is currently challenging due to its heterogeneity. Many autoantibodies are associated with SLE and are considered potential diagnostic markers, but systematic screening and validation of such autoantibodies is lacking. This study aimed to systematically discover new autoantibodies that may be good biomarkers for use in SLE diagnosis. METHODS: Sera from 15 SLE patients and 5 healthy volunteers were analysed using human proteome microarrays to identify candidate SLE-related autoantibodies. The results were validated by screening of sera from 107 SLE patients, 94 healthy volunteers and 60 disease controls using focussed arrays comprised of autoantigens corresponding to the identified candidate antibodies. Logistic regression was used to derive and validate autoantibody panels that can discriminate SLE disease. Extensive ELISA screening of sera from 294 SLE patients and 461 controls was performed to validate one of the newly discovered autoantibodies. RESULTS: A total of 31, 11 and 18 autoantibodies were identified to be expressed at significantly higher levels in the SLE group than in the healthy volunteers, disease controls and healthy volunteers plus disease control groups, respectively, with 25, 7 and 13 of these differentially expressed autoantibodies being previously unreported. Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. Some associations were seen with clinical characteristics of SLE patients, such as disease activity with the level of anti-PARP1 and rash with the level of anti-RPLP2, anti-MAK16 and anti- RPL7A. CONCLUSION: The combined autoantibody panels identified here show promise for the diagnosis of SLE and for differential diagnosis of other major rheumatic immune diseases.

Increased circulating CXCL13 levels in systemic lupus erythematosus and rheumatoid arthritis: a meta-analysis.

OBJECTIVES: CXC ligand 13 (CXCL13) is known as B cell chemotactic factor (BLC), promoting the migration of B lymphocytes by communicating with its receptor CXCR5, which can be regarded as part of pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). This meta-analysis was to evaluate the circulating CXCL13 levels in SLE and RA. METHODS: All articles were respectively gathered from PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) (by the end of 10 April 2019). According to random effects model, standardized mean difference (SMD) and 95% confidence interval (CI) of CXCL13 levels in SLE and RA were calculated by Stata 12.0 software. RESULTS: Totally, 15 studies were selected (981 SLE patients and 380 healthy controls, 332 RA patients and 147 healthy controls). SLE and RA patients were significantly increased in circulating CXCL13 levels (SMD = 1.851, 95% CI 0.604-3.098; SMD = 1.801, 95% CI = 1.145-2.457). Subgroup analyses showed that SLE patients from the Chinese group and systemic lupus erythematosus disease activity index (SLEDAI) score ≥ 6 group had higher circulating CXCL13 levels (SMD = 2.182, 95% CI 0.135-4.229; SMD = 0.767, 95% CI 0.503-1.030). However, there were no significant changes in CXCL13 concentrations in SLE patients from the English and SLEDAI score < 6 group. Similarly, subgroup analyses presented that RA patients from different classifications showed higher circulating CXCL13 levels. There was no publication bias. CONCLUSIONS: This meta-analysis demonstrated increased circulating CXCL13 concentrations in SLE and RA patients. Circulating CXCL13 levels may act as biomarkers and therapy targets in the diagnosis and treatment of SLE and RA.Key Point• First, CXC ligand 13 (CXCL13) is closely related to the pathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), Second, this study may provide novel therapeutic targets for the treatment of SLE and RA patients. This meta-analysis provides a comprehensive analysis of circulating CXCL13 levels in patients with SLE and RA and also explores related influencing factors.