scholarly journals Methylation Pattern of the SOCS3 and IL6R Promoters in Rheumatoid Arthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Marek Cieśla ◽  
Bogdan Kolarz ◽  
Maria Majdan ◽  
Dorota Darmochwał-Kolarz
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Methylation Status ◽  
Joint Destruction ◽  
Methylation Pattern ◽  
Cytokine Signaling ◽  
Healthy Controls ◽  
Promoter Regions ◽  
Specific Pcr ◽  
Genes Encoding

Interleukin-6 (IL-6) plays an essential function in the development of rheumatoid arthritis (RA), mainly through its proinflammatory effect, which may lead to joint destruction. The genes encoding IL-6 receptor (IL6R) and suppressor of cytokine signaling 3 (SOCS3) play a key role in the IL-6 signaling pathway, but their epigenetic regulation remains unclear. The aim of the study was to investigate how the presence of methylation in the SOCS3 and IL6R promoters is associated with the morbidity and severity of RA. A total of 146 unrelated individuals, 122 with RA and 24 healthy controls, were enrolled in the study. All subjects were genotyped with regard to the rs4969168 and rs4969170 polymorphisms in the SOCS3 gene and the rs2228145 and rs4129267 polymorphisms in IL6R. The methylation study included 52 patients with RA and 24 healthy controls. Qualitative real-time methylation-specific PCR was used to evaluate methylation status. We found no differences between patients and healthy controls in the methylation pattern in the IL6R and SOCS3 promoter regions and in variants frequency. The methylation profiles of the SOCS3 and IL6R promoters do not support the hypothesis that the genes SOCS3 and IL6R involved in the JAK-STAT signaling pathway are epigenetically deregulated in whole blood.

scholarly journals A DNA-Methylated Sight on Autoimmune Inflammation Network across RA, pSS, and SLE

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Xingqiang Wang ◽  
Dongyun Lei ◽  
Jie Ding ◽  
Shuang Liu ◽  
Li Tao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Lupus Erythematosus ◽  
Inflammatory Process ◽  
Methylation Status ◽  
Differential Methylation ◽  
Promoter Regions ◽  
Bioinformatics Analyses ◽  
Epigenetic Biomarkers ◽  
The Difference ◽  
Autoimmune Tautology

Methylation variabilities of inflammatory cytokines play important roles in the development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjögren’s syndrome (pSS). With heightened focus on personalized and precise medicine, it is necessary to compare and contrast the difference and similarity of cytokine methylation status between the 3 most classic autoimmune diseases (AIDs). In this study, we integrated 5 Cytokine-Chips from genome-wide DNA methylation datasets of the 3 kind of AIDs, delta-beta value was calculated for intergroup difference, and comprehensive bioinformatics analyses of cytokine genes with aberrant methylations were performed. 125 shared differential methylation variabilities (DMVs) were identified. There were 102 shared DMVs with similar methylation status; 3 hypomethylated differential methylation regions (DMRs) across the AIDs were found, and all 3 DMRs were hypomethylated. DMRs (AZU1, LTBR, and RTEL1) were likely to serve as activator in the inflammatory process. Particularly, AZU1 and LTBR with hypomethylated TSS and first exon located in the promoter regions were able to trigger inflammation signaling cascades and play critical roles in autoimmune tautology. Moreover, functional epigenetic module (FEM) algorithm showed that different inflammatory networks are involved in different AIDs; 5 hotspots were identified as biologically plausible pathways in inducing or perpetuating of inflammation which are epigenetically deregulated in AIDs. We concluded methylation variabilities among the same cytokines can greatly impact the perpetuation of inflammatory process or signal pathway of AIDs. Differentiating the cytokine methylation status will serve as valuable resource for researchers alike to gain better understanding of the epigenetic mechanisms of the three AIDs. Even more importantly, better understanding of cytokine methylation variability existing between the three classic AIDs will aid in identification of potential epigenetic biomarkers and therapeutic targets. This trial is registered with ChiCTR-INR-16010290, a clinical trial for the treatment of rheumatoid arthritis with Warming yang and Smoothening Meridians.

scholarly journals Proteomics Approach for the Discovery of Rheumatoid Arthritis Biomarkers Using Mass Spectrometry

2019 ◽  
Vol 20 (18) ◽  
pp. 4368 ◽  
Author(s):  
Mun ◽  
Lee ◽  
Park ◽  
Kim ◽  
Lee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mass Spectrometry ◽  
Vitamin D ◽  
Binding Protein ◽  
Joint Destruction ◽  
Protein Profiling ◽  
Serum Amyloid ◽  
Healthy Controls ◽  
Vitamin D Binding Protein ◽  
Proteomics Approach

Rheumatoid arthritis is an autoimmune disease that causes serious functional loss in patients. Early and accurate diagnosis of rheumatoid arthritis may attenuate its severity. Despite a diagnosis guideline in the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis, the practical difficulties in its diagnosis highlight the need of developing new methods for diagnosing rheumatoid arthritis. The current study aimed to identify rheumatoid arthritis diagnostic biomarkers by using a proteomics approach. Serum protein profiling was conducted using mass spectrometry, and five distinguishable biomarkers were identified therefrom. In the validation study, the five biomarkers were quantitatively verified by multiple reaction monitoring (MRM) analysis. Two proteins, namely serum amyloid A4 and vitamin D binding protein, showed high performance in distinguishing patients with rheumatoid arthritis from healthy controls. Logistic analysis was conducted to evaluate how accurately the two biomarkers distinguish patients with rheumatoid arthritis from healthy controls. The classification accuracy was 86.0% and 81.4% in patients with rheumatoid arthritis and in healthy controls, respectively. Serum amyloid A4 and vitamin D binding protein could be potential biomarkers related to the inflammatory response and joint destruction that accompany rheumatoid arthritis.

scholarly journals Genome-Wide DNA Methylation Pattern in Whole Blood Associated With Primary Intracerebral Hemorrhage

2021 ◽  
Vol 12 ◽  
Author(s):  
Yupeng Zhang ◽  
Hongyu Long ◽  
Sai Wang ◽  
Wenbiao Xiao ◽  
Meishan Xiong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Intracerebral Hemorrhage ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Methylation Status ◽  
Methylation Pattern ◽  
Healthy Controls ◽  
Differentially Methylated Genes ◽  
Dna Methylation Pattern ◽  
Methylation Patterns

Primary intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality throughout the world. ICH is a multifactorial disease that emerges from interactions among multiple genetic and environmental factors. DNA methylation plays an important role in the etiology of complex traits and diseases. We used the Illumina Infinium Human Methylation 850k BeadChip to detect changes in DNA methylation in peripheral blood samples from patients with ICH and healthy controls to explore DNA methylation patterns in ICH. Here, we compared genomic DNA methylation patterns in whole blood from ICH patients (n = 30) and controls (n = 34). The ICH and control groups showed significantly different DNA methylation patterns at 1530 sites (p-value < 5.92E-08), with 1377 hypermethylated sites and 153 hypomethylated sites in ICH patients compared to the methylation status in healthy controls. A total of 371 hypermethylated sites and 35 hypomethylated sites were in promoters, while 738 hypermethylated sites and 67 hypomethylated sites were in coding regions. Furthermore, the differentially methylated genes between ICH patients and controls were largely related to inflammatory pathways. Abnormalities in the DNA methylation pattern identified in the peripheral blood of ICH patients may play an important role in the development of ICH and warranted further investigation.

scholarly journals THU0024 METHYLATION ANALYSIS OF VITAMIN D SIGNALING PATHWAY GENES IN RHEUMATOID ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 225.1-225
Author(s):  
E. Punceviciene ◽  
J. Gaizevska ◽  
R. Sabaliauskaite ◽  
L. Venceviciene ◽  
D. Vitkus ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Methylation ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Methylation Level ◽  
Methylation Pattern ◽  
Healthy Controls ◽  
Methylation Analysis ◽  
Vitamin D Metabolism ◽  
Significant Difference

Background:Vitamin D is known for its immunomodulatory and epigenome interacting effects. Vitamin D deficiency is frequently observed in rheumatoid arthritis (RA) patients compared to healthy controls, is also named as a potential risk factor in RA ethiopatogenesis and may alter DNA methylation of certain genes [1,2]. Still, causality of vitamin D deficiency in RA patients needs to be elucidated.Objectives:The aim of the study was to evaluate relationship between DNA methylation status of vitamin D related genes (VDR,CYP24A1,CYP2R1), miRNA-155 expression, vitamin D level and its association with RA.Methods:CpG islands in promoter region of theVDR,CYP24A1,CYP2R1genes were chosen for DNA methylation analysis by means of pyrosequencing. DNA from blood mononuclear cells of 31 RA patients and 31 age and sex matched healthy controls was assessed for methylation pattern after informed consent was obtained in Vilnius university Hospital Santaros klinikos Centre of Rheumatology. For miRNA analysis quantitative reverse transcription PCR was used. Chemiluminescent microplate immunoassay was used to asses 25(OH)D serum levels.Results:25(OH)D concentrations varied from deficiency (<50 nmol/l), insufficiency (50-75 nmol/l) to normal range (≥75-100 nmol/l) in RA (mean 47.49 nmol/l; SD ± 27.93) and healthy controls (mean 57.38 nmol/l; SD ± 29.93)).CYP24A1methylation level was significantly higher in comparison toVDR(p<0.0001) andCYP2R1(p<0.0001) genes in both groups.CYP24A1hypermethylation was also observed in older subjects (p=0.012). The study demonstrated a significant positive correlation between vitamin D concentration andVDR,CYP2R1genes methylation intensity (r2=0.31, p=0.014; r2=0.25, p=0.042, respectively). However, gene methylation frequency and methylation intensity showed no significant difference between RA patients and healthy controls (VDR– 2.4vs2.6 %,CYP24A1– 16.6vs15.3 %,CYP2R1– 2.6vs2.6 %) (p>0.05). To note, miRNA-155 expression negatively correlated withCYP24A1methylation intensity (r2=-0.43, p=0.009).Conclusion:Our study identified significant associations between theVDRandCYP2R1promoter methylation and vitamin D concentration. However, no significant differences in DNA methylation pattern between RA patients and healthy controls were detected. MiR-155 expression was associated withCYP24A1methylation level, confirming its possible involvement in vitamin D metabolism. The data of our study suggests that epigenetic phenomena are significantly involved in vitamin D metabolism and may have an indirect effect on RA ethiopatogenesis.References:[1]Jeffery LE, et al. Nat Rev Rheumatol. 2016,12.4:201.[2]Fetahu IS et al. Front Physiol. 2014,5:164.Acknowledgments:This project has received funding from the Research Council of Lithuania (LMTLT), agreement No. S-MIP-17-12.Disclosure of Interests:None declared

scholarly journals Integration of Transcriptome and Methylome Analyses Provides Insight Into the Pathway of Floral Scent Biosynthesis in Prunus mume

2021 ◽  
Vol 12 ◽  
Author(s):  
Xi Yuan ◽  
Kaifeng Ma ◽  
Man Zhang ◽  
Jia Wang ◽  
Qixiang Zhang
Keyword(s):  
Dna Methylation ◽  
Epigenetic Modification ◽  
Floral Scent ◽  
Methylation Status ◽  
Enrichment Analysis ◽  
Biosynthesis Pathway ◽  
Prunus Mume ◽  
Promoter Regions ◽  
Differentially Methylated Genes ◽  
Genes Encoding

DNA methylation is a common epigenetic modification involved in regulating many biological processes. However, the epigenetic mechanisms involved in the formation of floral scent have rarely been reported within a famous traditional ornamental plant Prunus mume emitting pleasant fragrance in China. By combining whole-genome bisulfite sequencing and RNA-seq, we determined the global change in DNA methylation and expression levels of genes involved in the biosynthesis of floral scent in four different flowering stages of P. mume. During flowering, the methylation status in the “CHH” sequence context (with H representing A, T, or C) in the promoter regions of genes showed the most significant change. Enrichment analysis showed that the differentially methylated genes (DMGs) were widely involved in eight pathways known to be related to floral scent biosynthesis. As the key biosynthesis pathway of the dominant volatile fragrance of P. mume, the phenylpropane biosynthesis pathway contained the most differentially expressed genes (DEGs) and DMGs. We detected 97 DMGs participated in the most biosynthetic steps of the phenylpropane biosynthesis pathway. Furthermore, among the previously identified genes encoding key enzymes in the biosynthesis of the floral scent of P. mume, 47 candidate genes showed an expression pattern matching the release of floral fragrances and 22 of them were differentially methylated during flowering. Some of these DMGs may or have already been proven to play an important role in biosynthesis of the key floral scent components of P. mume, such as PmCFAT1a/1c, PmBEAT36/37, PmPAL2, PmPAAS3, PmBAR8/9/10, and PmCNL1/3/5/6/14/17/20. In conclusion, our results for the first time revealed that DNA methylation is widely involved in the biosynthesis of floral scent and may play critical roles in regulating the floral scent biosynthesis of P. mume. This study provided insights into floral scent metabolism for molecular breeding.

scholarly journals Inhibition of the IL-18 Receptor Signaling Pathway Ameliorates Disease in a Murine Model of Rheumatoid Arthritis

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 11 ◽  
Author(s):  
Yuji Nozaki ◽  
Jinhai Ri ◽  
Kenji Sakai ◽  
Kaoru Niki ◽  
Koji Kinoshita ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Bone Erosion ◽  
Quantitative Polymerase Chain Reaction ◽  
Joint Inflammation ◽  
Type Ii Collagen ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cytokine Signaling ◽  
Pro Inflammatory Cytokines

Interleukin (IL)-18 expression in synovial tissue correlates with the severity of joint inflammation and the levels of pro-inflammatory cytokines. However, the role of the IL-18/IL-18 receptor-alpha (Rα) signaling pathway in autoimmune arthritis is unknown. Wild-type (WT) and IL-18Rα knockout (KO) mice were immunized with bovine type II collagen before the onset of arthritis induced by lipopolysaccharide injection. Disease activity was evaluated by semiquantitative scoring and histologic assessment. Serum inflammatory cytokine and anticollagen antibody levels were quantified by an enzyme-linked immunosorbent assay. Joint cytokine and matrix metalloproteinases-3 levels were determined by a quantitative polymerase chain reaction. Splenic suppressors of cytokine signaling (SOCS) were determined by Western blot analysis as indices of systemic immunoresponse. IL-18Rα KO mice showed lower arthritis and histological scores in bone erosion and synovitis due to reductions in the infiltration of CD4+ T cells and F4/80+ cells and decreased serum IL-6, -18, TNF, and IFN-γ levels. The mRNA expression and protein levels of SOCS3 were significantly increased in the IL-18Rα KO mice. By an up-regulation of SOCS, pro-inflammatory cytokines were decreased through the IL-18/IL-18Rα signaling pathway. These results suggest that inhibitors of the IL-18/IL-18Rα signaling pathway could become new therapeutic agents for rheumatoid arthritis.

scholarly journals OP0184 PHENOTYPING OF MOLECULAR SIGNATURES IN THE SYNOVIAL TISSUE OF RHEUMATOID ARTHRITIS BY INTEGRATIVE SYSTEMS ANALYSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 111-112
Author(s):  
J. Qiao ◽  
S. X. Zhang ◽  
H. Wang ◽  
J. Q. Zhang ◽  
M. T. Qiu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Signaling Pathway ◽  
Systems Analysis ◽  
Joint Destruction ◽  
Functional Enrichment ◽  
Shanxi Province ◽  
Molecular Signatures ◽  
Disease Heterogeneity ◽  
Synovial Tissues

Background:Rheumatoid arthritis (RA) is an aggressive immune-mediated joint disease characterized by synovial proliferation and inflammation, cartilage destruction, and joint destruction1. Despite efforts to characterize the disease subsets and to predict the differential prognosis in RA patients, disease heterogeneity is not adequately translated into the current clinical subclassification2.Objectives:To develop and validate an integrative system approach for stratifying patients with RA according to disease status and whole-genome gene expression data.Methods:An RNA sequencing dataset of synovial tissues from 124 RA patients (including 57 patients with early RA, 95 with established RA) and 15 healthy controls (HC) was imported from the Gene Expression Omnibus (GEO) database (GSE89408) by software package R (version 4.0.3). After filtrating of differentially expressed genes (DEGs) between RA and HC, non-negative matrix factorization, functional enrichment, and immune cell infiltration were applied to illustrate the landscapes of these patients for classification. Clinical features (age, gender, and auto-antibodies) were also compared to discover the signatures of these classifications.Results:A matrix of 576 DEGs from RA samples was classified into 5 subtypes (early/C1–C3, established/C4-C5) with distinct molecular and cellular signatures and two sub-groups (S1 and S2) (Figure 1A-1D). New-onset patients (early C2) and established C4 patients were named as S1, they shared similar gene signatures mainly characterized by prominent immune cells and proinflammatory signatures, and enriched in the chemokine-mediated signaling pathway, lymphocyte activation, response to bacterium and Primary immunodeficiency. S2(C1, C3 and C5) were more occupied by synovial fibroblasts of destructive phenotype. They were mainly enriched in the response to external factors and PPAR signaling pathway (Figure 1E-1H). Interestingly, combined with clinical information, S1 and S2 had no significance in age and gender (P > 0.05). But patients in S1 had a stronger association with the presence of anti-citrullinated protein antibodies (ACPA) (P < 0.05) (Figure 1I-1J).Conclusion:We successfully deconvoluted RA synovial tissues into pathobiological discrete subsets using an unsupervised machine learning method and described their distinct molecular and cellular characteristics. These results provide important insights into divergent and shared mechanistic features of RA and serve as a template for future studies to guide drug tar-get discovery by synovial molecular signatures and de-sign stratified approaches for patients with RA.References:[1]Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet 2016;388(10055):2023-38. doi: 10.1016/S0140-6736(16)30173-8 [published Online First: 2016/10/30][2]Jung SM, Park KS, Kim KJ. Deep phenotyping of synovial molecular signatures by integrative systems analysis in rheumatoid arthritis. Rheumatology (Oxford) 2020 doi: 10.1093/rheumatology/keaa751 [published Online First: 2020/11/25]Acknowledgements:This project was supported by National Science Foundation of China (82001740), Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

scholarly journals Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis

2015 ◽  
Vol 112 (8) ◽  
pp. 2509-2514 ◽  
Author(s):  
Raphael Sanches Peres ◽  
Foo Y. Liew ◽  
Jhimmy Talbot ◽  
Vanessa Carregaro ◽  
Rene D. Oliveira ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Regulatory T Cells ◽  
Joint Destruction ◽  
Healthy Controls ◽  
Suppressive Activity ◽  
First Line Therapy ◽  
Noninvasive Biomarker ◽  
A Prospective Study ◽  
Low Expression

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by joint destruction and severe morbidity. Methotrexate (MTX) is the standard first-line therapy of RA. However, about 40% of RA patients are unresponsive to MTX treatment. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) are thought to play an important role in attenuating RA. To investigate the role of Tregs in MTX resistance, we recruited 122 RA patients (53 responsive, R-MTX; 69 unresponsive, UR-MTX) and 33 healthy controls. Three months after MTX treatment, R-MTX but not UR-MTX showed higher frequency of peripheral blood CD39+CD4+CD25+FoxP3+ Tregs than the healthy controls. Tregs produce adenosine (ADO) through ATP degradation by sequential actions of two cell surface ectonucleotidases: CD39 and CD73. Tregs from UR-MTX expressed a lower density of CD39, produced less ADO, and had reduced suppressive activity than Tregs from R-MTX. In a prospective study, before MTX treatment, UR-MTX expressed a lower density of CD39 on Tregs than those of R-MTX or control (P < 0.01). In a murine model of arthritis, CD39 blockade reversed the antiarthritic effects of MTX treatment. Our results demonstrate that MTX unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production. Our findings thus provide hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Furthermore, our data suggest that low expression of CD39 on Tregs could be a noninvasive biomarker for identifying MTX-resistant RA patients.

scholarly journals The Correlation Between Plasma Levels of Vitamin D and Epigenetic Alterations of Treg-Specific Demethylated Region (TSDR) in Rheumatoid Arthritis Patients

2019 ◽  
Author(s):  
Mahdi Taghadosi ◽  
Soraya Bilvayeh ◽  
Sasan Ghaffari ◽  
Nasrin Iranshahi ◽  
Amirreza Esfandiari ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Immune Responses ◽  
Plasma Levels ◽  
Foxp3 Expression ◽  
Healthy Controls ◽  
Epigenetic Alterations ◽  
Specific Pcr ◽  
Autoimmune Inflammatory Disease ◽  
25 Oh Vitamin D

Abstract- Rheumatoid arthritis (RA) is the most common autoimmune inflammatory disease of joints among adults. Regulatory T cells (Treg) control immune responses in this illness. Through the expression of FoxP3, a Treg transcription factor, Vitamin D keeps autoimmune diseases in check. Yet, the molecular mechanism of FoxP3 expression by vitamin D is not well-inspected. It may influence FoxP3 expression via epigenetic changes. This study aimed to investigate the correlation between plasma levels of vitamin D and the demethylation of the TSDR region in Foxp3 promoter in patients with RA. Twenty untreated RA patients and 41 healthy controls participated in this study. Plasma levels of 25-OH vitamin D were measured by competitive ELISA method. The demethylation of TSDR regions in Foxp3 gene was also assessed using the quantitative Methylation Specific PCR (qMSP) method. The demethylation of TSDR region was significantly lower in RA patients compared with healthy controls (P=0.006). Vitamin D plasma levels were significantly higher in RA patients rather than healthy people (P=0.034). There was no statistically significant correlation between vitamin D plasma levels and demethylation of TSDR region. As expected, epigenetic alternation showed considerable difference between RA patients and healthy controls, but about vitamin D correlation with methylation modification, more studies are needed

scholarly journals THU0104 THE GUT MICROBIOTA AND ITS RELEVANCE TO PERIPHERAL T REGULATORY CELLS AND T HELPER 17 IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 266.1-266
Author(s):  
Y. LI ◽  
S. X. Zhang ◽  
X. F. Yin ◽  
Z. Mingxing ◽  
J. Luo ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Gut Microbiota ◽  
Lymphocyte Subsets ◽  
Joint Destruction ◽  
Absolute Number ◽  
P Value ◽  
Rrna Gene ◽  
Healthy Controls ◽  
The Absolute

Background:Rheumatoid arthritis (RA) is a common autoimmune disorder with joint destruction and synovial inflammation characterized by abnormal immune responses to autoantigens. Our previous studies have demonstrated that impaired peripheral lymphocytes especially insufficiency of regulatory T cells (Tregs) played an important role in pathogenesis of RA1 2. Interestingly, the dysbiosis of gut microbiota triggers several types of autoimmune diseases through the imbalance of T lymphocyte subsets3. However, the detailed gut microbiota of RA patients and its correlation with Tregs and helper T cells 17 (Th17) are unclear up until now.Objectives:To compare the difference of gut microbiota between RA and healthy controls (HCs), and to investigate the relevance of gut microbiota with circulating Tregs and Th17 in patients with RA.Methods:From December 2018 to August 2019, a total of 205 diagnosed patients with RA and 199 age and sex-matched HCs were enrolled in this study. Stool of Every participant was collected for bacterial DNA extraction and 16S ribosomal RNA (rRNA) gene sequencing. The absolute numbers of Tregs and Th17 in PB of these individuals were measured by Flow Cytometer (FCM) combined with standard absolute counting beads. Data were expressed as mean ± standard deviation to the distribution. Independent-samples T test and Spearman rank correlation test. P value <0.05 were considered statistically significant.Results:Patients with RA had a significantly difference of diversity and abundance of intestinal microbiota compared with those of HCs (P< 0.05). Detailedly, the abundance of Proteobacteria was significantly increased in RA patients (P< 0.05), and the abundance of Firmicutes, Fusobacteria and Verrucomicrobia were significantly reduced (P<0.05) at the level of Phylum (Figure 1). At the genus level, in the RA group, the abundance of Escherichia, Ruminococcus2 and Clostridium_sensu_stricto were significantly increased (P< 0.05), but the abundance of Lachnospiracea_incertae_sedis, Prevotella, Clostridium_XlVa, Roseburia, Dialister, Blautia, Megamonas and Gemmiger were significantly lower than the healthy controls (P< 0.05) (Figure 2). Moreover, Blautia, Anaerostipes and Ruminococcus2 have negative correlation with the absolute number of Tregs, and Cloacibacillus and Streptophyta have positive correlation with the absolute number of Th17.Conclusion:Patients with RA had a dysbiosis of the gut microbiota in both diversity and abundance, which is closely related to the impaired peripheral lymphocyte subsets, that may be related to the pathogenesis of RA, which might provide a new idea for RA treatment.References:[1]Wen HY, Wang J, Zhang SX, et al. Low-Dose Sirolimus Immunoregulation Therapy in Patients with Active Rheumatoid Arthritis: A 24-Week Follow-Up of the Randomized, Open-Label, Parallel-Controlled Trial.J Immunol Res2019;2019:7684352. doi: 10.1155/2019/7684352 [published Online First: 2019/11/30][2]Niu HQ, Li ZH, Zhao WP, et al. Sirolimus selectively increases circulating Treg cell numbers and restores the Th17/Treg balance in rheumatoid arthritis patients with low disease activity or in DAS28 remission who previously received conventional disease-modifying anti-rheumatic drugs.Clin Exp Rheumatol2019 [published Online First: 2019/05/11][3]Lee N, Kim WU. Microbiota in T-cell homeostasis and inflammatory diseases.Exp Mol Med2017;49(5):e340. doi: 10.1038/emm.2017.36 [published Online First: 2017/05/27]Acknowledgments:NoneDisclosure of Interests:None declared

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