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 Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients

2017 ◽  
Vol 42 (2) ◽  
pp. 651-659 ◽  
Author(s):  
Qingqing Ouyang ◽  
Jing Wu ◽  
Zhenlan Jiang ◽  
Jinjun Zhao ◽  
Ran Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood Mononuclear Cells ◽  
Roc Curve ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Circular Rnas ◽  
Screening Methods ◽  
Roc Curve Analysis ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Background/Aims: Circular RNAs (circRNAs) compose a large class of RNAs that can be used as biomarkers in clinical blood samples. This study aimed to determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify novel biomarkers for RA screening. Methods: We started with a microarray screening of circRNA changes in PBMCs from 5 RA patients and 5 healthy controls. We then confirmed the selected circRNA changes in PBMCs from 30 RA patients and 25 age- and sex-matched controls using the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman correlation test was performed to assess the correlation of circRNAs and clinical variables. Receiver operating characteristic (ROC) curve was calculated to evaluate the diagnostic value. Results: We identified and verified five circRNAs (092516, 003524, 103047, 104871, 101873) that were significantly elevated in PBMCs from RA patients. Among these RA patients, we detected no significant correlation between the five circRNAs and the disease severity, including disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and health assessment questionnaire (HAQ). Yet, ROC curve analysis suggested that circRNA_104871 has significant value of RA diagnosis (AUC=0.833, P<0.001), followed by circRNA_003524 (AUC = 0.683, P = 0.020), circRNA_101873 (AUC = 0.676, P = 0.026), and circRNA_103047 (AUC = 0.671, P = 0.030). Conclusions: This study suggests that increased expression of circRNAs circRNA_104871, circRNA_003524, circRNA_101873 and circRNA_103047 in PBMC from RA patients may serve as potential biomarkers for RA patient diagnosis.

scholarly journals OP0033 REGULATORY T CELL CD39 EXPRESSION AS A PREDICTOR OF EARLY REMISSION-INDUCTION WITH METHOTREXATE IN NEW-ONSET RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 18.2-18
Author(s):  
P. Brown ◽  
A. Anderson ◽  
B. Hargreaves ◽  
A. Morgan ◽  
J. D. Isaacs ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Disease Modifying Therapy ◽  
Blood Mononuclear Cells ◽  
Treatment Naïve ◽  
Disease Modifying ◽  
Pre Treatment

Background:The long term outcomes for patients with rheumatoid arthritis (RA) depend on early and effective disease control. Methotrexate remains the key first line disease modifying therapy for the majority of patients, with 40% achieving an ACR50 on monotherapy(1). There are at present no effective biomarkers to predict treatment response, preventing effective personalisation of therapy. A putative mechanism of action of methotrexate, the potentiation of anti-inflammatory adenosine signalling, may inform biomarker discovery. By antagonism of the ATIC enzyme in the purine synthesis pathway, methotrexate has been proposed to increase the release of adenosine moieties from cells, which exert an anti-inflammatory effect through interaction with ADORA2 receptors(2). Lower expression of CD39 (a cell surface 5-’ectonucleotidase required for the first step in the conversion of ATP to adenosine) on circulating regulatory T-Lymphocytes (Tregs) was previously identified in patients already established on methotrexate who were not responding (DAS28 >4.0 vs <3.0)(3). We therefore hypothesised that pre-treatment CD39 expression on these cells may have clinical utility as a predictor of early methotrexate efficacy.Objectives:To characterise CD39 expression in peripheral blood mononuclear cells in RA patients naïve to disease modifying therapy commencing methotrexate, and relate this expression to 4 variable DAS28CRP remission (<2.6) at 6 months.Methods:68 treatment naïve early RA patients starting methotrexate were recruited from the Newcastle Early Arthritis Clinic and followed up for 6 months. Serial blood samples were taken before and during methotrexate therapy with peripheral blood mononuclear cells isolated by density centrifugation. Expression of CD39 by major immune subsets (CD4+ and CD8+ T-cells, B-lymphocytes, natural killer cells and monocytes) was determined by flow cytometry. The statistical analysis used was binomial logistic regression with baseline DAS28CRP used as a covariate due to the significant association of baseline disease activity with treatment response.Results:Higher pre-treatment CD39 expression was observed in circulating CD4+ T-cells of patients who subsequently achieved clinical remission at 6 months versus those who did not (median fluorescence 4854.0 vs 3324.2; p = 0.0108; Figure 1-A). This CD39 expression pattern was primarily accounted for by the CD4+CD25 high sub-population (median fluorescence 9804.7 vs 6455.5; p = 0.0065; Figure 1-B). These CD25 high cells were observed to have higher FoxP3 and lower CD127 expression than their CD39 negative counterparts, indicating a Treg phenotype. No significant associations were observed with any other circulating subset. A ROC curve demonstrates the discriminative utility of differential CD39 expression in the CD4+CD25 high population for the prediction of DAS28CRP remission in this cohort, showing greater specificity than sensitivity for remission prediction(AUC: 0.725; 95% CI: 0.53 - 0.92; Figure 1-C). Longitudinally, no significant induction or suppression of the CD39 marker was observed amongst patients who did or did not achieve remission over the 6 months follow-up period.Figure 1.Six month DAS28CRP remission versus pre-treatment median fluorescence of CD39 expression on CD4+ T-cells (A); CD25 High expressing CD4+ T-cells (B); and ROC curve of predictive utility of pre-treatment CD39 expression on CD25 High CD4+ T-cells (C).Conclusion:These findings support the potential role of CD39 in the mechanism of methotrexate response. Expression of CD39 on circulating Tregs in treatment-naïve RA patients may have particular value in identifying early RA patients likely to respond to methotrexate, and hence add value to evolving multi-parameter discriminatory algorithms.References:[1]Hazlewood GS, et al. BMJ. 2016 21;353:i1777[2]Brown PM, et al. Nat Rev Rheumatol. 2016;12(12):731-742[3]Peres RS, et al. Proc Natl Acad Sci U S A. 2015;112(8):2509-2514Disclosure of Interests:None declared

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