scholarly journals AB0020 CORRELATION BETWEEN SERUM AND SYNOVIAL CONCENTRATION OF IL-17A AND MIRNA EXPRESSION IN RHEUMATOID ARTHRITIS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1313.2-1313
Author(s):  
R. Shumnalieva ◽  
D. Kachakova ◽  
T. Velikova ◽  
R. Kaneva ◽  
Z. Kolarov ◽  
...  

Background:Interleukin 17 (IL-17) is a proinflammatory cytokine, which overproduction promotes the autoimmune reaction in rheumatoid arthritis (RA). Posttranscriptional regulation of IL-17 by specific microRNAs (miRNAs) is of great interest in the recent years. 146a was associated with IL-17 expression in IL-17 producing T-cells in the synovium when miR-155 enhanced Treg and Th17 cells differentiation and IL-17A production by directly targeting the suppressor of cytokine signaling (SOCS) 1 [1, 2]. It has been shown that IL-17 production in lymphocytes or its function could be regulated by miR-223 by targeting Roquin ubiquitin ligase or its receptors [3].Objectives:To examine a possible correlation between systemic and local concentrations of IL-17A and systemic and local miR-146a, miR-155 and miR-223 expression in RA patients.Methods:Expression levels of three miRNAs were determined in matched peripheral blood (PB) and synovial fluid (SF) samples of RA patients by relative quantitation method 2-ΔΔCt. As reference control for normalization RNU6B gene was used. Concentrations of IL-17A were compared between matched serum and SF samples from 20 RA patients by Human IL-17A ELISA kit (Gene probe, Diaclone, France). Healthy donors were used as controls.Results:miR-146a, miR-155 and miR-223 showed overexpression in RA SF when compared to HCs SF (in 70.83%, p=0.007; in 79.17%, p=1.63x10-4and in 79.17%, p=1.64x10-3, respectively). The ROC curve analysis showed diagnostic accuracy for miR-146a in SF with AUC=0.769, p=0.006, AUC for SF miR-155 was 0.858, p=2.3x10-4and AUC for SF miR-223 was 0.841 p=4.6x10-4. SF levels of miR-146a and miR-155 were overexpressed in 52.17% and in 76.09% of the RA patients compared to its systemic levels. SF miR-223 was underexpressed in 58.7% of the patients compared to its systemic levels. Levels of IL-17A were higher in RA SF compared to serum (8.645 pg/ml versus 0.315 pg/ml, p=0.012). ROC curve analysis for SF IL-17A showed area under the curve (AUC) = 0.885, p<0.000.Conclusion:The difference between the systemic and local concentration of IL-17A and miRNAs expression shows that the inflammatory disease process leads to their altered expression with a possible role of these molecules in the disease pathogenesis. The higher local levels of miR-155, miR-146 and IL-17A confirm the data about the possible role of these miRNAs in regulating IL-17A production. The opposite changes of IL-17A and miR-223 systemic and local levels confirm the data about the possible role of miR-223 in regulating IL-17 function. Further analysis with larger sets is needed to confirm these results.References:[1]Niimoto T, Nakasa T, Ishikawa M, Okuhara A, Izumi B, Deie M, et al. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord. 2010; 11:209.[2]Yao R, Ma YL, Liang W, Li HH, Ma ZJ, Yu X. et al. MicroRNA-155 modulates Treg and Th17 cells differentiation and Th17 cell function by targeting SOCS1. PLoS ONE 2012; 7(10):e46082.[3]Schaefer J, Nakra N, Montufar-Solis D, Vigneswaran N, Klein J. Role for miR-223 and Roquin in IL-10 mediated regulation of IL-17. J Immunol. 2013; 190 (1 Supplement) 171.9.Acknowledgments:The study was supported by Grant 14-D/2012, Grant 60/2013 and Grant 61/2015 from Medical University-Sofia, BulgariaDisclosure of Interests:None declared

2021 ◽  
Vol 26 (Supplement_1) ◽  
pp. e39-e41
Author(s):  
Lilian Kebaya ◽  
Mong Tieng Ee ◽  
Michael Miller ◽  
Soume Bhattacharya

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Hypoxic-ischemic encephalopathy (HIE) is a major contributor to morbidity and mortality. Therapeutic hypothermia (TH) is the standard of care for neonates with moderate to severe HIE. Brain magnetic resonance imaging (MRI) is the imaging modality of choice for confirmation of HIE, assessment of injury severity, and prognostication. Reliable, inexpensive and widely available laboratory measures for early identification of risk for neurological injury can play a critical role in the optimal management of neonatal HIE, especially in the resource-limited setting. Our study examined whether derangements in early routine laboratory measures (acid-base, haematological, metabolic) were worse in neonates with MRI findings of neurological injury. Objectives Primary objective: To evaluate the role of early laboratory measures in predicting neurological injury as detected by MRI at 72 hours. Secondary objective: To evaluate the role of early laboratory measures in predicting survival to NICU discharge in patients with HIE. Design/Methods This single-centre, retrospective cohort study included neonates ≥ 35 weeks gestation with moderate to severe HIE, who had undergone therapeutic hypothermia. Based on findings of brain MRI completed within 72 hours of life, our cohort was divided into 2 groups: neonates with, and without, evidence of neurological injury consistent with HIE. Baseline characteristics, as well as laboratory measures, were compared between groups, and a receiver operating characteristic (ROC) curve analysis was conducted to determine the cut-off for prediction of neurological injury based on the highest sensitivity and specificity values. Results 104 neonates were analyzed. Baseline characteristics (Table 1) were similar between both groups, except for cord venous pH and base excess (BE), which were significantly lower in the abnormal MRI group (p = 0.02). In bivariate analysis, pH (at 1 h of age, p = 0.027), BE (at 1 h, p = 0.001, and 6 h of age, p = 0.004), ionized calcium (at 6 h of age, p = 0.02), and platelets (at 1 h of age, p = 0.004) were significantly different in neonates with abnormal MRI. In ROC curve analysis, BE at 1 h of life was the best predictor of abnormal MRI (AUC = 0.71, p = 0.002), with a cut-off value of ≤ -14.95, sensitivity of 67% and specificity of 66% (Figure 1). Conclusion Among neonates with HIE undergoing TH, early laboratory measures such as acid-base status, ionized calcium, and platelet count were worse in neonates with abnormal MRI, in comparison to neonates with normal MRI. Base excess at 1 h of life is a good predictor of abnormal MRI. Future prospective studies to validate these findings are needed


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Takeki Hata ◽  
Masafumi Takahashi ◽  
Masanori Kawaguchi ◽  
Yuichiro Kashima ◽  
Yuji Shiba ◽  
...  

Background: Accumulating evidence indicates that CD4 + T cells contribute to the development of collateral vesssels in ischemic tissue; however, little is known about the responsible subset of CD4 + T cells in the induction of angiogenesis. Th17 cells are recently identified as a new subset of CD4 + T cells and have been associated with the pathogenesis of certain autoimmune diseases. Th17 cells specifically secrete interleukin-17 (IL-17) and regulate various biological functions. The purpose of this study is to investigate the role of CD4 + T and Th17 cells in angiogenic response to hindlimb ischemia. Methods and Results: Unilateral hindlimb ischemia was produced in wild-type (WT: C57BL/6, 8- to 10-week-old) mice treated with or without a neutralizing antibody against CD4. Blood flow perfusion and capillary formation were assessed by using a laser Doppler perfusion imaging (LDPI) and CD31 immunostaining, respectively. Well-developed collateral vessels and capillary formation were observed in WT mice in response to hindlimb ischemia. Treatment with a neutralizing anti-CD4 antibody resulted in almost complete CD4 + T cell depletion (flow cytometry analysis, control: 45.4% vs. antibody: 1.0%) and a significant decrease in angiogenesis after the induction of hindlimb ischemia (LDPI, 21 days, control: 0.61 ± 0.1 vs. antibody: 0.41 ± 0.1, p<0.05). IL-17-deficient (IL-17 −/− ) mice also showed a significant reduction of blood flow perfusion, compared with WT mice (LDPI, day 14: 0.56 ± 0.3 vs. 0.31 ± 0.2, p<0.05; day 21: 0.66 ± 0.3 vs. 0.37 ± 0.3, p=0.05). IL-17 −/− mice had severe ischemic damage of the limb and resulted in a 25% incidence of autoamputation by day 21 (no limb loss in WT mice). Furthermore, capillary formation was also decreased significantly in IL-17 −/− mice (692.9 ± 165.6/mm 2 vs. 1223.3 ± 267.3/mm 2 , p<0.01). Conclusion : These findings demonstrate that Th17 cells, a new subset of CD4 + T cells, contribute to the angiogenic response to hindlimb ischemia and provide new insights into the mechanism by which T cells promote collateral development and angiogenesis.


2019 ◽  
Vol 45 (04) ◽  
pp. 348-355
Author(s):  
Gao Zhao-wei ◽  
Guan-hua Zhao ◽  
Rui-cheng Li ◽  
Hui-ping Wang ◽  
Chong Liu ◽  
...  

Abstract Objective The aim of this study was to evaluate the changes and diagnostic value of serum ADA activity in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and myasthenia gravis (MG). Methods Serum ADA activity, including total ADA (tADA) and its isoenzymes (ADA1 and ADA2), was determined in patients with different autoimmune diseases (144 RA, 114 SLE, 55 AS, 68 MG). The changes in serum ADA activity in patients were analysed. A receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic performance of serum ADA activity. Results Compared with healthy controls, the serum tADA activity in SLE patients was significantly increased (p<0.001), while the serum tADA activity in patients with RA, AS and MG did not change (p>0.05). The ROC analysis showed that the optimal cut-off value of serum tADA activity for SLE diagnosis was 10.5 U/L (79.8% specificity and 74.6% sensitivity; likelihood ratio (LR): 3.693; p<0.001). Moreover, our results showed that there were no significant changes of ADA1 and ADA2 activity in RA, AS and MG patients, while the serum ADA2 activity was significantly increased in SLE patients. The ROC analysis showed that ADA2 activity could be used in diagnosing SLE with 75.4% specificity and 78.1% sensitivity (LR: 3.175). Based on the ROC curve analysis, serum tADA activity (79.8% specificity and 74.6% sensitivity; likelihood ratio (LR): 3.693) and ADA2 activity (75.4% specificity and 78.1% sensitivity; LR: 3.175) are unlikely to be used in diagnosing SLE. Furthermore, there was a positive correlation between tADA activity and SLE disease activity (r=0.303, p=0.010). Notably, serum tADA activity in SLE patients with arthritis was higher than in patients without arthritis (p=0.005), which suggests that tADA activity might be related to lupus arthritis. Conclusion These findings suggest that serum tADA and ADA2 activity might play an important role in SLE progression.


2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Taku Kuwabara ◽  
Fumio Ishikawa ◽  
Motonari Kondo ◽  
Terutaka Kakiuchi

Interleukin-17 (IL-17) induces the production of granulocyte colony-stimulating factor (G-CSF) and chemokines such as CXCL1 and CXCL2 and is a cytokine that acts as an inflammation mediator. During infection, IL-17 is needed to eliminate extracellular bacteria and fungi, by inducing antimicrobial peptides such as defensin. This cytokine also plays an important role in chronic inflammation that occurs during the pathogenesis of autoimmune diseases and allergies such as human rheumatoid arthritis (RA) for which a mouse model of collagen-induced arthritis (CIA) is available. In autoimmune diseases such as RA and multiple sclerosis (MS), IL-17 is produced by helper T (Th) cells that are stimulated by IL-1βand IL-6 derived from phagocytes such as macrophages and from tissue cells. IL-17 contributes to various lesions that are produced by Th17 cells, one subset of helper T cells, and byγδT cells and innate lymphoid cells. It strongly contributes to autoimmune diseases that are accompanied by chronic inflammation. Thus, a functional understanding of Th17 cells is extremely important. In this review, we highlight the roles of cytokines that promote the development and maintenance of pathogenic Th17 cells in autoimmune diseases.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1116.2-1116
Author(s):  
Y. Ben Abderrazek ◽  
R. Dhahri ◽  
W. Lahmar ◽  
M. Slouma ◽  
B. Louzir ◽  
...  

Background:The role of rheumatoid arthritis as an ischemic heart disease and heart failure risk factor is well acknowledged even if the physiopathological pathways are still debated. The effect of anemia on myocardial deformation has already been established and a hemoglobin level below 9g/dL was associated with a significantly lower global longitudinal strain (GLS) patients with no history of CVD or chronic inflammatory diseases.[1]Objectives:In the present study, we looked into the effect of anemia and hemoglobin on the myocardial impairement in RA patients.Methods:We conducted a monocentric cross-sectional study between march 2019 and september 2019 on 36 RA patients without any history of cardiovascular disease and non-altered left ventricular ejection fraction in the outpatient population of the rheumatology department of the military hospital of Tunis matched with 36 healthy control subjects. Both groups underwent conventional echocardiography and STE to measure GLS; subclinical left ventricular systolic dysfunction was defined as a GLS > −18%, and a complete blood cell count; anemia was defined as Hemoglobin levels < 12 g/dL for women and < 13 g/dL for men.Results:Myocardial deformation study revealed that rheumatoid arthritis patients had a significantly worse GLS than healthy controls (18.99±2.81% vs 20.42±1.33%; P=.015). We also observed that third of the RA patients had subclinical left ventricular systolic dysfunction.In our report 36% of RA patients were anemic. In our univariate analysis anemia was found to be significantly correlated with GLS (r=−0.368, P=.027) and hemoglobin was found to be the best predictor of subclinical LVSD in our ROC curve analysis (AUC=0.752, 95% CI: 0.577-0.927, P=.02). In our multivariate analysis anemia was the only factor that was independently related to subclinical LVSD (OR: 11.39, 95% CI: 1.57-82.89, P=.016).Figure 1.ROC curve analysis for Hemoglobin as a predictor of subclinical left ventricular systolic dysfunctionConclusion:To our knowledge, this is the first study to look into the relationship between GLS and anemia among RA patients, and now it is safe to say that anemia is yet another added burden on the myocardial function in RA patients that needs to be taken into account when discussing therapeutic action.References:[1]Zhou Q, Shen J, Liu Y, Luo R, Tan B, Li G. Assessment of left ventricular systolic function in patients with iron deficiency anemia by three-dimensional speckle-tracking echocardiography. Anatol J Cardiol. 2017;18(3):194–9.Disclosure of Interests:None declared


2020 ◽  
Author(s):  
Marco Di Carlo ◽  
Marika Tardella ◽  
Emilio Filippucci ◽  
Marina Carotti ◽  
Fausto Salaffi

Abstract Background. In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. However, in patients with RA it is not yet clear how to interpret, in quantitative terms, the presence of B-lines, the LUS artifact indicative of ILD. The aim of this study was to determine the cut-off number of LUS B-lines that identifies a significant RA-ILD.Methods. A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence.Patients underwent LUS (carried out in 14 defined intercostal spaces), chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of chest HRCT using a computer-aided method (CaM). The discriminative validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis.Results. 72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years). The mean estimate of pulmonary fibrosis using the CaM was 11.20% (SD 7.48) at chest HRCT, while at LUS the mean number of B-lines was 10.65 (SD 15.11). A significant RA-ILD, as measured by the CaM at HRCT, was detected in 25 patients (34.7%). The presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant RA-ILD with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4.Conclusion. The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.


2021 ◽  
Vol 2021 ◽  
pp. 1-29
Author(s):  
Yongbin Jing ◽  
Dong Han ◽  
Chunyang Xi ◽  
Jinglong Yan ◽  
Jinpeng Zhuang

Background. The current study is aimed at identifying the cross-talk genes between periodontitis (PD) and rheumatoid arthritis (RA), as well as the potential relationship between cross-talk genes and pyroptosis-related genes. Methods. Datasets for the PD (GSE106090, GSE10334, GSE16134) and RA (GSE55235, GSE55457, GSE77298, and GSE1919) were downloaded from the GEO database. After batch correction and normalization of datasets, differential expression analysis was performed to identify the differentially expressed genes (DEGs). The cross-talk genes linking PD and RA were obtained by overlapping the DEGs dysregulated in PD and DEGs dysregulated in RA. Genes involved in pyroptosis were summarized by reviewing literatures, and the correlation between pyroptosis genes and cross-talk genes was investigated by Pearson correlation coefficient. Furthermore, the weighted gene coexpression network analysis (WGCNA) was carried out to identify the significant modules which contained both cross-talk genes and pyroptosis genes in both PD data and RA data. Thus, the core cross-talk genes were identified from the significant modules. Receiver-operating characteristic (ROC) curve analysis was performed to identify the predictive accuracy of these core cross-talk genes in diagnosing PD and RA. Based on the core cross-talk genes, the experimentally validated protein-protein interaction (PPI) and gene-pathway network were constructed. Results. A total of 40 cross-talk genes were obtained. Most of the pyroptosis genes were not differentially expressed in disease and normal samples. By selecting the modules containing both cross-talk genes or pyroptosis genes, the blue module was identified to be significant module. Three genes, i.e., cross-talk genes (TIMP1, LGALS1) and pyroptosis gene-GPX4, existed in the blue module of PD network, while two genes (i.e., cross-talk gene-VOPP1 and pyroptosis gene-AIM2) existed in the blue module of RA network. ROC curve analysis showed that three genes (TIMP1, VOPP1, and AIM2) had better predictive accuracy in diagnosing disease compared with the other two genes (LGALS1 and GPX4). Conclusions. This study revealed shared mechanisms between RA and PD based on cross-talk and pyroptosis genes, supporting the relationship between the two diseases. Thereby, five modular genes (TIMP1, LGALS1, GPX4, VOPP1, and AIM2) could be of relevance and might serve as potential biomarkers. These findings are a basis for future research in the field.


2021 ◽  
Author(s):  
Zhijian Wang ◽  
Xuenuo Chen ◽  
Zheng Jiang

Abstract Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a dismal prognosis according to updated statistics. At present, there are many deficiencies in targeted therapy for liver cancer. The solute carrier family 17 member 2 (SLC17A2) has not been studied in liver cancer, therefore, we evaluate the role of SLC17A2 in HCC by bioinformatics analysis.Methods: The expression level of SLC17A2 in HCC, the clinicopathological data were analyzed based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, the SLC17A2 protein expression was validated by immunohistochemical staining. Besides, the Kaplan–Meier plotter database and receiver operating characteristic (ROC) curve analysis were used to explore the prognostic significance. The biological analyses of SLC17A2 were performed using the gene set enrichment analysis (GSEA). Finally, Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to explore the relationship between immune cell infiltration, immune cell markers and SLC17A2 in HCC.Results: The multivariate Cox regression analysis showed that SLC17A2 expression was low in HCC (P < 0.05), and closely related to the clinical stage of HCC. Besides, SLC17A2 had certain prognostic and diagnostic value in HCC according to ROC curve analysis. Further biological analyses showed that SLC17A2 can regulate fatty acid metabolism, amino acid metabolism and cytochrome P450-related metabolism and is closely related to the peroxisome pathway. Notably, we found that SLC17A2 expression was positively correlated with the infiltration levels of CD4 + T cells, naive CD8+ T cells, naive B cells, negatively associated with the levels of regulatory T cells and closely correlated with most immune cell markers in HCC.Conclusion: SLC17A2 expression is low in HCC and correlates with immune infiltration; thus, it could serve as an independent prognostic factor for HCC.


2020 ◽  
Author(s):  
Marco Di Carlo ◽  
Marika Tardella ◽  
Emilio Filippucci ◽  
Marina Carotti ◽  
Fausto Salaffi

Abstract Background In recent years, a growing interest has grown around interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). While high resolution computed tomography (HRCT) of the chest remains the diagnostic method of choice, increasing attention has been directed towards lung ultrasound (LUS) in the diagnosis of ILD in connective tissue diseases. However, it is not yet well defined how to interpret the LUS findings under suspicion of RA-ILD. The aim of this study was to determine the cut-off number of LUS B-lines that identifies a significant RA-ILD. Methods A cross sectional study was conducted on consecutive RA patients with suspected RA-ILD. The inclusion criteria were clinical (dyspnea, velcro sounds), instrumental (suggestive anomalies on conventional radiography, DLco reduction), or in presence of at least two of the following risk factors for RA-ILD: smoking habit, male sex, advanced age, and ACPA presence. Patients underwent LUS (carried out in 14 defined intercostal spaces), chest HRCT, pulmonary function tests, and clinical evaluation. The diagnosis of RA-ILD was based on a semi-quantitative evaluation of chest HRCT using a computer-aided method (CaM). The discriminative validity of the LUS versus HRCT has been studied by using the receiver operating characteristic (ROC) curve analysis. Results 72 consecutive RA patients (21 male, 51 female) were evaluated, with a mean age of 63.0 (SD 11.5 years). The mean estimate of pulmonary fibrosis using the CaM was 11.20% (SD 7.48) at chest HRCT, while at LUS the mean number of B-lines was 10.65 (SD 15.11). A significant RA-ILD, as measured by the CaM at HRCT, was detected in 25 patients (34.7%). The presence of 9 B-lines was found to be the optimal cut-off at ROC curve analysis. This LUS cut-off defines the presence of significant RA-ILD with a sensitivity of 70.0%, a specificity of 97.62%, and a positive likelihood ratio of 29.4. Conclusion The present study provided data to determine the number of B-lines to identify a significant RA-ILD. LUS may represent a useful technique to select RA patients to be assessed by chest HRCT.


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