IntroductionIncreasing evidence indicates that microRNAs (miRNAs) play a critical role in the pathogenesis of inflammatory diseases. The aim of the study was to investigate the expression pattern and function of miRNAs in CD4+ T cells from patients with rheumatoid arthritis (RA).MethodsThe expression profile of miRNAs in CD4+ T cells from synovial fluid (SF) and peripheral blood of 33 RA patients was determined by microarray assay and validated by qRT-PCR analysis. The correlation between altered expression of miRNAs and cytokine levels was determined by linear regression analysis. The role of miR-146a overexpression in regulating T cell apoptosis was evaluated by flow cytometry. A genome-wide gene expression analysis was further performed to identify miR-146a-regulated genes in T cells.ResultsmiRNA expression profile analysis revealed that miR-146a expression was significantly upregulated while miR-363 and miR-498 were downregulated in CD4+ T cells of RA patients. The level of miR-146a expression was positively correlated with levels of tumor necrosis factor-alpha (TNF-α), and in vitro studies showed TNF-α upregulated miR-146a expression in T cells. Moreover, miR-146a overexpression was found to suppress Jurkat T cell apoptosis. Finally, transcriptome analysis of miR-146a overexpression in T cells identified Fas associated factor 1 (FAF1) as a miR-146a-regulated gene, which was critically involved in modulating T cell apoptosis.ConclusionsWe have detected increased miR-146a in CD4+ T cells of RA patients and its close correlation with TNF-α levels. Our findings that miR-146a overexpression suppresses T cell apoptosis indicate a role of miR-146a in RA pathogenesis and provide potential novel therapeutic targets.
Genetics alone cannot explain most cases of rheumatoid arthritis (RA). Thus, investigating environmental factors such as the gut microbiota may provide new insights into the initiation and progression of RA. In this study, we performed 16S rRNA sequencing to characterise the gut microbiota of DBA1 mice that did or did not develop arthritis after induction with collagen. We found that divergence in the distribution of microbiota after induction was pronounced and significant. Mice susceptible to collagen-induced arthritis (CIA) showed enriched operational taxonomic units (OTUs) affiliated with the genus Lactobacillus as the dominant genus prior to arthritis onset. With disease development, the abundance of OTUs affiliated with the families Bacteroidaceae, Lachnospiraceae, and S24-7 increased significantly in CIA-susceptible mice. Notably, germ-free mice conventionalized with the microbiota from CIA-susceptible mice showed a higher frequency of arthritis induction than those conventionalized with the microbiota from CIA-resistant mice. Consistently, the concentration of the cytokine interleukin-17 in serum and the proportions of CD8+T cells and Th17 lymphocytes in the spleen were significantly higher in the former group, whereas the abundances of dendritic cells, B cells, and Treg cells in the spleen were significantly lower. Our results suggest that the gut microbiome influences arthritis susceptibility.
The objective of this study was to analyze human fecal Lactobacillus community and its relationship with rheumatoid arthritis. Samples taken from rheumatoid arthritis (RA) patients and healthy individuals were analyzed by quantitative real-time PCR. Bacterial DNA was extracted from feces, and amplicons of the Lactobacillus-specific regions of 16S rRNA were analyzed by denaturing gradient gel electrophoresis. The richness, Shannon-Wiener index, and evenness of gut microbiota of both groups were analyzed to compare fecal Lactobacillus community structures. Results of this study demonstrated that fecal microbiota of RA patients contained significantly more Lactobacillus (10.62 ± 1.72 copies/g) than the control group (8.93 ± 1.60 copies/g). Significant increases were observed in RA patients in terms of the richness, Shannon-Wiener, and evenness measures, indicating more bacterial species, and increased bacterial diversity and abundance. These results suggest a potential relationship between Lactobacillus communities and the development and progression of rheumatoid arthritis.
Osteoarthritis (OA) is a degenerative disease of middle-aged and elderly people, contributed a higher burden of disease in China and the world. In 2017, under the support of the Rheumatology and Immunology Expert Committee of the Cross-Strait Medical and Health Exchange Association. The objective was to develop an evidence-based diagnosis and treatment guideline for OA in China based on emerging new evidence. The guideline was registered at International Practice Guidelines Registry Platform (IPGRP-2018CN028). The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence and the strength of recommendations, and the RIGHT (Reporting Items for Practice Guidelines in Healthcare) checklist was followed to report the guideline. The guideline provides recommendations for the OA diagnosis, disease risks monitoring and evaluate, treatment purpose and physical, medical and surgical interventions. This guideline is intended to serve as a tool for Chinese clinicians for the best decisions-making on diagnosis and treatment of OA.
Background: Rheumatoid arthritis patients are at higher risk of developing comorbidities. The main objective of this study was to evaluate the prevalence of major comorbidities in Chinese rheumatoid arthritis patients. We also aimed to identify factors associated with these comorbidities. Methods: Baseline demographic, clinical characteristics and comorbidity data from RA patients enrolled in the Chinese Registry of rhEumatoiD arthrITis (CREDIT) from Nov 2016 to August 2017 were presented and compared with those from five other registries across the world. Possible factors related to three major comorbidities (cardiovascular disease, fragility fracture and malignancy) were identified using multivariate logistic regression analyses. Results: A total of 13,210 RA patients were included (80.6% female, mean age 52.9 years and median RA duration 4.0 years). Baseline prevalence rates of major comorbidities were calculated: CVD, 2.2% (95% CI 2.0-2.5%); fragility fracture, 1.7% (95% CI 1.5-1.9%); malignancy, 0.6% (95% CI 0.5-0.7%); overall major comorbidities, 4.2% (95% CI 3.9-4.6%). Advanced age was associated with all comorbidities. Male gender and disease duration were positively related to CVD. Female sex and longer disease duration were potential risk factors for fragility fractures. Ever use of methotrexate (MTX) was negatively related to baseline comorbidities. Conclusions: Patients with rheumatoid arthritis in China have similar prevalence of comorbidities with other Asian countries. Advanced age and long disease duration are possible risk factors for comorbidities. On the contrary, MTX may protect RA patients from several major comorbidities, supporting its central role in the management of rheumatoid arthritis.
Objective. To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans.Methods. A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations.Results. Three non-major histocompatibility complex (non-MHC) loci were identified at the genomewide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These
Objective. The inflammasome-related protein NLRP1/NALP1 has been implicated in the onset and progression of some autoimmune diseases. This study was undertaken to determine whether a polymorphism in the NLRP1 gene is associated with susceptibility to rheumatoid arthritis (RA) in Han Chinese and to assess the functional implications of this association.Methods. RA patients (n ؍ 190) and matched healthy controls (n ؍ 190) residing in the city of Chengdu were genotyped for the NLRP1 promoter polymorphisms rs6502867 and rs878329. Genotyping for rs878329 was performed in a second set of subjects (n ؍ 1,514) residing in the city of Chongqing. The effect of each polymorphism on NLRP1 transcription was evaluated by dual-luciferase assay, while the effect on DNA protein interaction was determined by electrophoretic mobility shift assay. Differential expression of NLRP1 in individuals with different genotypes was investigated by real-time quantitative polymerase chain reaction.Results. The polymorphism rs878329, but not rs6502867, was associated with RA (odds ratio [OR] 0.83, P ؍ 0.02 for the C allele; OR 0.42, P ؍ 0.01 for the CC genotype). The GG genotype of rs878329 was the risk genotype for RA (OR 2.38) and had a runt-related transcription factor 1 binding site that up-regulated NLRP1 transcription. Individuals with the RA risk genotype GG had significantly higher NLRP1 messenger RNA levels than those with the CC genotype among the Han Chinese population.Conclusion. Our findings indicate that NLRP1 is associated with RA in Han Chinese. The G allele of rs878329 in the NLRP1 promoter up-regulates gene transcription and confers the risk of RA.
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