scholarly journals miRNA-485-5p, an Inflammation-Related microRNA, May be a Diagnostic Biomarker of Rheumatoid Arthritis

2021 ◽  
Author(s):  
Dan Jiang ◽  
Ximing Zheng ◽  
Jian Chen ◽  
Aijun Zhang ◽  
Guangxian Xu
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Roc Curves ◽  
Autoimmune Disorder ◽  
Healthy Controls ◽  
Diagnostic Biomarker ◽  
Peripheral Blood Mononuclear ◽  
Das 28 ◽  
The Impact

Abstract Background Rheumatoid arthritis (RA) is a chronic systematic autoimmune disorder that is characterized by symmetrical and inflammatory destruction of distal joints. Dysregulation of microRNAs(miRNAs) are frequently involved in inflammation, and can contribute to pathogenesis and progression of RA. This study aimed to investigate the expression of multiple inflammation-related miRNAs of RA patients and the latent mechanism, and identify novel diagnostic biomarkers. Methods Samples of 100 patients with RA and 72 healthy controls were included. The expression of predicted inflammation-related miRNAs, including miR-16, miR-17, miR-132, miR-140, miR-150, miR-181, miR-200-c, miR-203, miR-223 and miR-485-5p and RA associated genes, including IL-17, IL-18, DAS-28, MMP3, TLR-4, IRAK-4 in plasma and peripheral blood mononuclear cells (PBMCs) of RA patients compared with healthy controls (HC), were detected by qRT-PCR and ELISA. The interaction between miR-485-5p and TLR-4 or IRAK-4 was verified through dual luciferase report assays, western-blot and correlation analysis. The potential of miR-485-5p to be a biomarker for RA diagnostics was valued by ROC curves. Results Among the differentially expressed miRNAs, the expression of miR-485-5p exhibited significantly lower in plasma and PBMCs of the RA patients and was well relevant in the various body fluid samples. The expression of miR-485-5p was negatively correlated with the expression of DAS-28, IL-17, IL-18 and MMP-3, which are significant features of RA. Moreover, the ROC curve of plasma and PBMC miR-485-5p for RA revealed a high diagnostic accuracy. Furthermore, miR-485-5p could inhibit the expression of inflammatory cytokines in macrophages by targeting TLR4 and IRAK4, and the expression of miR-485-5p negatively correlated with the level of TLR4 and IRAK4 in the plasma of RA. Conclusion Collectively, our results indicated that down-expression of miR-485-5p was remarkably related to the deterioration of RA progression via the impact on inflammatory cytokines in macrophages, and may serve as a potential diagnostic biomarker and therapeutic target for RA.

scholarly journals Gene-regulatory network study of rheumatoid arthritis in single-cell chromatin landscapes of peripheral blood mononuclear cells

2021 ◽  
Author(s):  
Cantong Zhang ◽  
Xiaoping Hong ◽  
Haiyan Yu ◽  
Hongwei Wu ◽  
Huixuan Xu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Single Cell ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
High Resolution Map ◽  
The Impact ◽  
Accessible Chromatin

Abstract Rheumatoid arthritis is a chronic autoinflammatory disease with an elusive etiology. Assays for transposase-accessible chromatin with single-cell sequencing (scATAC-seq) contribute to the progress in epigenetic studies. However, the impact of epigenetic technology on autoimmune diseases has not been objectively analyzed. Therefore, scATAC-seq was performed to generate a high-resolution map of accessible loci in peripheral blood mononuclear cells (PBMCs) of RA patients at the single-cell level. The purpose of our project was to discover the transcription factors (TFs) that were involved in the pathogenesis of RA at single-cell resolution. In our research, we obtained 22 accessible chromatin patterns. Then, 10 key TFs were involved in the RA pathogenesis by regulating the activity of MAP kinase. Consequently, two genes (PTPRC, SPAG9) regulated by 10 key TFs were found that may be associated with RA disease pathogenesis and these TFs were obviously enriched in RA patients (p<0.05, FC>1.2). With further qPCR validation on PTPRC and SPAG9 in monocytes, we found differential expression of these two genes, which were regulated by eight TFs (ZNF384, HNF1B, DMRTA2, MEF2A, NFE2L1, CREB3L4 (var. 2), FOSL2::JUNB (var. 2), MEF2B). What is more, the eight TFs showed highly accessible binding sites in RA patients. These findings demonstrate the value of using scATAC-seq to reveal transcriptional regulatory variation in RA-derived PBMCs, providing insights on therapy from an epigenetic perspective.

scholarly journals Using protein microarray reveals clinical correlation between self-perception of patient and the apoptosis-related proteins in rheumatoid arthritis

2020 ◽  
Author(s):  
Jian-ting Wen ◽  
Jian Liu ◽  
Hui Jiang ◽  
Lei Wan ◽  
Ling Xin ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Controls ◽  
Self Perception ◽  
Roc Curve Analysis ◽  
Peripheral Blood Mononuclear ◽  
Related Proteins ◽  
Potential Biomarkers

Abstract Background: The most severe effects of rheumatoid arthritis (RA) are loss of physical function, which may have a significant impact on self-perception of patient (SPP). However, the inherent relationship between SPP and the key proteins is not clear. The aim of this study was to get an insight into SPP of RA in connection with the the apoptosis-related proteins. Methods: We set out to investigate changes of the apoptosis-related proteins expression in the peripheral blood mononuclear cells (PBMCs) of RA. Additionally, we aimed to correlate the apoptosis-related proteins expression profiles with SPP and clinical indexes. To this end, we employed antibody microarrays of the the apoptosis-related proteins in PBMCs from four RA patients and seven healthy controls. We used bioinformatics to screen several the apoptosis-related proteins. To validate key protein candidates, we performed Enzyme linked immunosorbent assay (ELISA) on 30 RA patients and 30 healthy controls. Results: We found the expression of ten the apoptosis-related proteins (caspase3, CD40, SMAC, HSP27, HTRA, IGFBP-1, IGFBP-6, sTNF-R1, sTNF-R2, TRAILR-3) were significantly altered in PBMCs of RA patients. Receiver operating characteristic (ROC) curve analysis suggested that these ten the apoptosis-related proteins are potential biomarkers of RA. Spearman Correlation analysis and Logistic-regression analysis revealed that the 10 selected the apoptosis-related proteins correlated with SPP and clinical indexes. Conclusion: Therefore, we highlight some the apoptosis-related proteins may serve as potential biomarkers in prediction of SPP for RA patients, although the underlying mechanisms need to be further explored.

scholarly journals The Increased RNase Activity of IRE1α in PBMCs from Patients with Rheumatoid Arthritis

2019 ◽  
Vol 9 (3) ◽  
pp. 505-509 ◽  
Author(s):  
Mahdieh Ahmadiany ◽  
Mahshid Alavi-Samani ◽  
Zahra Hashemi ◽  
Mohammad Amin Moosavi ◽  
Marveh Rahmati
Keyword(s):  
Rheumatoid Arthritis ◽  
Er Stress ◽  
Mononuclear Cells ◽  
Gradient Centrifugation ◽  
Rnase Activity ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Micro Rnas ◽  
Density Gradient Centrifugation Method ◽  
Gene Expression Levels

Purpose: Despite recent advances in the diagnosis and treatment of rheumatoid arthritis (RA), this inflammatory disease remains a challenge to patients and physicians. Recent evidence highlights the contribution of endoplasmic reticulum (ER) stress in the pathogenesis and treatment of RA. Herein, we study the expression of the ER stress sensor inositol-requiring enzyme 1α (IRE1α), as well as XBP1 splicing and the regulated IRE1-dependent decay (RIDD), in peripheral blood mononuclear cells (PBMCs) from patients with RA compared with healthy controls. Methods: The PBMCs from blood samples of RA patients and healthy volunteers were isolated by a density gradient centrifugation method using Ficoll. The gene expression levels of GRP78/ Bip, IRE1, XBP1s, micro-RNAs (miRNAs) were evaluated by real-time PCR. Results: The expression of GRP78, IRE1, and XBP1s were increased in PBMCs of RA patients compared with healthy controls. We further show that the RIDD targets (miRNA-17, -34a, -96, and -125b) were downregulated in RA samples. Conclusion: This study can expand our knowledge on the importance of RNase activity of IRE1α in RA and may offer new potentials for developing novel diagnostic and/or therapeutic biomarkers.

scholarly journals Circulating MicroRNA-21 Is a Potential Diagnostic Biomarker in Gastric Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jianhong Wu ◽  
Guangxin Li ◽  
Zeyou Wang ◽  
Yongliang Yao ◽  
Rui Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Sensitivity And Specificity ◽  
Mononuclear Cells ◽  
Early Stage ◽  
Stage Iv ◽  
Clinicopathological Features ◽  
Circulating Microrna ◽  
Healthy Controls ◽  
Diagnostic Biomarker ◽  
Peripheral Blood Mononuclear

MicroRNA-21 was upexpressed in gastric cancer (GC) indicating that it is a potential diagnostic biomarker for GC. In this study, 50 GC patients and 50 healthy controls were recruited. miR-21 levels in serum and peripheral blood mononuclear cells (PBMCs) were quantified using quantitative real-time PCR. CA199, and CEA were measured using electrochemiluminescence assay. The sensitivity and specificity of circulating miR-21, CA199 and CEA in GC diagnosis, the correlation of circulating miR-21 to clinicopathological features, and the diagnostic value of miR-21 in different GC stages were determined. The levels of miR-21 in both serum and PBMCs increased significantly in GC patients comparing to healthy controls; however, no correlation was observed between circulating miR-21 level and clinicopathological features. The sensitivity and specificity of miR-21 in serum and PBMCs, and CA199 and CEA in GC diagnosis were 88.4%, 79.6%, 81.3%, 73.4%, 60.5%, 55.9%, and 68.6%, 59.3%, respectively. The positive prediction rates of circulating miR-21 in GC stages I to IV were all around 90%, while those of CA199 and CEA were around or less than 50%. Our data suggest circulating miR-21 (both in serum and in PBMCs) can serve as a good biomarker for GC and could be used in diagnosis of early (stage I) and late GC (stage IV).

Genetic association of ankylosing spondylitis with TBX21 influences T-bet and pro-inflammatory cytokine expression in humans and SKG mice as a model of spondyloarthritis

2016 ◽  
Vol 76 (1) ◽  
pp. 261-269 ◽  
Author(s):  
Max C Lau ◽  
Patricia Keith ◽  
Mary-Ellen Costello ◽  
Linda A Bradbury ◽  
Kelly A Hollis ◽  
...  
Keyword(s):  
T Cells ◽  
Ankylosing Spondylitis ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Joint Inflammation ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Adaptive Immune Cells ◽  
Cd69 Expression ◽  
The Impact

ObjectivesAnkylosing spondylitis (AS) is a highly heritable immune-mediated arthropathy. Inflammation in AS is poorly understood. TBX21 encodes T-bet, a transcription factor, lying within a locus with genome-wide significant association with AS. T-bet is implicated in innate and adaptive immunity. However, the role of T-bet in AS pathogenesis is unclear.MethodsWe assessed the importance of T-bet in disease development and progression in peripheral blood mononuclear cells from 172 AS cases and 83 healthy controls carrying either risk or protective alleles of the peak AS-associated TBX21 single nucleotide polymorphism. Kinetics and localisation of T-bet expression in the SKG mouse model of spondyloarthropathy was examined, along with the impact of Tbx21 knockout on arthritis development in SKG mice.ResultsPatients with AS had higher T-bet expression than healthy individuals, driven predominantly by natural killer and CD8+ T cells, with expression levels in CD8+ T cells completely distinguishing AS cases from healthy controls. T-bet expression was increased in AS cases carrying risk compared with protective alleles of rs11657479. In curdlan-treated SKG mice, T-bet expression increased early after disease initiation and persisted throughout the course of disease. There was marked reduction in gut and peripheral joint inflammation, and less IFNγ-producing and IL-17-producing CD8+ T cells, in Tbx21−/− compared with wild-type SKG mice.ConclusionsAS-associated variants in TBX21 influence T-bet expression. T-bet+ innate and adaptive immune cells have altered IL-17 and IFNγ, and early activation marker CD69 expression than T-bet cells. This indicates that T-bet is a major component of inflammatory pathways of spondyloarthropathy in humans and mice.

scholarly journals Identification of circular RNAs hsa_circ_0140271 in peripheral blood mononuclear cells as a novel diagnostic biomarker for female rheumatoid arthritis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yufeng Chen ◽  
Xianghe Xu ◽  
Xuegang Li ◽  
Junlong Zhong ◽  
Biao Wu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Fatty Acid ◽  
Potential Role ◽  
Acid Metabolism ◽  
Mononuclear Cells ◽  
Circular Rnas ◽  
Diagnostic Biomarker ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Microrna Sponge

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease, which commonly affects women. Accumulating evidence shows that differentially expressed circular RNAs (circRNAs) play crucial roles in the progress of RA. However, the roles of circRNAs in female RA remains unclear. This study explores potential role and diagnostic value of hsa_circ_0140271 from peripheral blood mononuclear cells (PBMC) in female RA. Methods Differential expression of circRNAs was determined by RNA-sequencing in PBMC from 4 healthy controls (HC) and 4 RA patients, and we further measured the level of hsa_circ_0140271 in a validation cohort consisting of 47 RA and 47 HC via RT-qPCR. Besides, correlation studies with clinical variables were also examined. What’s more, we performed bioinformatics analysis to predict the potential role of hsa_circ_0140271. Results PBMC expression of hsa_circ_0140271 of female RA was significantly higher than that of female HC, and it was positively correlated with antistreptolysin (ASO). Furthermore, the receiver operating characteristic (ROC) curve indicated that hsa_circ_0140271 could distinguish female RA from female HC and female patients with ankylosing spondylitis (AS) or osteoarthritis (OA). Besides, the combined diagnosis anti-cyclic citrullinated peptide (Anti-CCP) + hsa_circ_0140271 could improve diagnostic accuracy with an area under the curve (AUC) of 0.818 to compared with Anti-CCP. Furthermore, KEGG pathway enrichment analysis indicated hsa_circ_0140271 may act as microRNA sponge and participate in fatty acid metabolism pathways. Conclusion Hsa_circ_0140271 was likely to be used as a promising diagnostic biomarker for female RA; it may act as microRNA sponge to regulate fatty acid metabolism pathways in RA.

scholarly journals Distinctive Expression of Bone Metabolism-related Genes between PBMCs from Condylar Hyperplasia, Rheumatoid Arthritis, and Ankylosing Spondylitis Patients

2020 ◽  
Author(s):  
Reza Amirzargar ◽  
Gholamreza Shirani ◽  
Shokoufeh Raisian ◽  
Maryam Davoudi ◽  
Saeed Aslani ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Bone Metabolism ◽  
Bone Morphogenetic Proteins ◽  
Mononuclear Cells ◽  
Healthy Controls ◽  
Messenger Rnas ◽  
Healthy Individuals ◽  
Peripheral Blood Mononuclear ◽  
Condylar Hyperplasia

Bone morphogenetic proteins (BMPs) and wingless (Wnt) signaling molecules and their antagonists, such as sclerostin and noggin, have been identified to have different effects on bone metabolism. This research intended to evaluate the transcript levels of CTNNB1 (catenin beta 1protein), SOST (sclerostin protein), BMP4 (Bone Morphogenetic Protein 4 protein), and NOG (noggin protein) bone metabolism-related genes in peripheral blood mononuclear cells (PBMCs) from condylar hyperplasia (CH) patients in comparison to rheumatoid arthritis (RA), ankylosing spondylitis (AS), and healthy individuals. PBMCs were separated from blood samples of 10 patients with CH, AS, RA, and 10 healthy controls. SYBR Green real-time polymerase chain reaction (PCR) was used for quantitative analysis of CTNNB1, SOST, BMP4, and NOG messenger RNAs (mRNAs). The expression of CTNNB1 was significantly upregulated in CH and AS patients compared with healthy individuals and RA patients. The difference of SOST expression was not significant between all groups. The BMP4 expression was significantly downregulated in AS, CH, and RA patients compared with healthy controls. The NOG expression was downregulated in RA, AS, and CH groups, however, it was only significant in CH and RA patients compared with controls.CH and AS patients were distinguished from RA by the upregulatedCTNNB1 expression. These results demonstrated that CTNNB1, BMP4, and NOG, but not SOST, may contribute to the pathogenesis of CH, AS, and RA.

scholarly journals Differentially Expressed Genes of Natural Killer Cells Can Distinguish Rheumatoid Arthritis Patients from Healthy Controls

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 492 ◽  
Author(s):  
Noha Mousaad Elemam ◽  
Mahmood Yaseen Hachim ◽  
Suad Hannawi ◽  
Azzam A. Maghazachi
Keyword(s):  
Rheumatoid Arthritis ◽  
Nk Cells ◽  
Natural Killer ◽  
Differentially Expressed Genes ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Protective Role ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear

Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases, while its molecular triggers are not fully understood. A few studies have shown that natural killer (NK) cells may play either a pathogenic or a protective role in RA. In this study, we sought to explore NK cell markers that could be plausibly used in evaluating the differences among healthy controls and RA patients. Publicly available transcriptome datasets from RA patients and healthy volunteers were analyzed, in order to identify differentially expressed genes (DEGs) between 1. different immune cells as compared to NK cells, and 2. NK cells of RA patients and healthy controls. The identified DEGs were validated using 16 healthy controls and 17 RA patients. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll density gradient method, while NK cells were isolated using RosetteSep technique. RNA was extracted and gene expression was assessed using RT-qPCR. All selected genes were differentially expressed in NK cells compared to PBMCs. CD56, CXCL16, PECAM-1, ITGB7, BTK, TLR10, and IL-1β were significantly upregulated, while CCL2, CCR4, RELA and IBTK were downregulated in the NK cells of RA patients when compared to healthy controls. Therefore, these NK specific genes might be used as promising biomarkers for RA diagnosis.

scholarly journals AB0107 INVESTIGATION OF THE EFFECTS OF KYNURENIC ACID ANALOGS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1352.1-1353
Author(s):  
B. Varga ◽  
A. Balog ◽  
F. Fülöp ◽  
L. Vécsei ◽  
Y. Mándi
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Kynurenic Acid ◽  
Mononuclear Cells ◽  
Activity Score ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Necrosis Factor

Background:The investigation of anti-inflammatory and immunosuppressive functions of kynurenic acid (KYNA) is now in focus. Previously, we demonstrated the opposite effects of KYNA and different KYNA analogs on tumor necrosis factor-α (TNF-α) production and tumor necrosis factor-stimulated gene-6 (TSG-6) expression in U-937 monocytic cells. The potential effect of KYNA analogs on further immune mediators including alarmins (S100A12=EN-RAGE and S100A8/9=calprotectin), and on human neutrofil peptide 1-3(α-defensin) production has not been investigated.Objectives:Therefore, in the present study, we compared the effects of newly synthesized KYNA analog on the TNF-α, alarmins and α-defensin production, correlation with the effects on the TSG-6 expression in rheumatoid arthritis (RA).Methods:93 RA patients were involved and divided subgroups based on DAS28 activity score. Peripheral blood mononuclear cells (PBMC) was isolated from RA patients and healthy controls. As cytokine inducers heat inactivatedStaphylococcus aureus(SA1) were used. In parallel in vitro experiments, the SA1 induced PBMCs were pretreated with a newly synthesized KYNA analog (compound SZR-72 was synthesized by direct amidation of KYNA). The concentrations of the above mentioned inflammatory mediators in the supernatants were quantified by using ELISA kits and the TSG-6 expression was also determined by RTqPCR method.Results:The SA1 induced TNF-α, EN-RAGE, calprotectin and α-defensin production was significantly higher in RA patients’ group than in healthy controls. KYNA analog attenuated the SA1 induced TNF-α, EN-RAGE, calprotectin and α-defensin production, and increased TSG-6 production and TSG-6 mRNA expression in PBMC cells from RA patients. The SA1 induced TNF-α and TSG-6 production correlated with the DAS28 activity score. The TNF-α inhibitory effect of the KYNA analog correlated inversely with the TSG-6 stimulatory effect in all subgroups of RA patients based on DAS28 activity score.Conclusion:TSG-6 expression could participate in the suppression of inflammatory cytokines, such as TNF-α, EN-RAGE, calprotectin and α-defensin. We suppose that the elevation of the TSG-6 expression by KYNA and especially by new KYNA analogs might be one of the mechanisms that are responsible for their suppressive effect on TNF-α production as a feedback mechanism in RA. KYNA and KYNA analogs have an important role in influencing TSG-6 expression, and there is a possible benefit with potential therapeutic consequence of targeting TSG-6 expression by kynurenines in inflammatory conditions in RA.References:[1]Mándi Y, Endrész V, Mosolygó T, Burián K, Lantos I, Fülöp F, Szatmári I, Lőrinczi B, Balog A, Vécsei L, The Opposite Effects of Kynurenic Acid and Different Kynurenic Acid Analogs on Tumor Necrosis Factor-a (TNF-a) Production and Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) Expression. Frontiers in Immunology. doi: 10.3389/fimmu.2019.01406Acknowledgments:This work was supported by GINOP 2.3.2-2015-16-00034Disclosure of Interests:None declared

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