Detection and Comparative Analysis of Methylomic Biomarkers of Rheumatoid Arthritis.
Ontology highlight
ABSTRACT:
SUBMITTER: Feng X
PROVIDER: S-EPMC7119472 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
Detection and Comparative Analysis of Methylomic Biomarkers of Rheumatoid Arthritis.
Feng Xin X Hao Xubing X Shi Ruoyao R Xia Zhiqiang Z Huang Lan L Yu Qiong Q Zhou Fengfeng F
Frontiers in genetics 20200327
Rheumatoid arthritis (RA) is a common autoimmune disorder influenced by both genetic and environmental factors. To investigate possible contributions of DNA methylation to the etiology of RA with minimum confounding genetic heterogeneity, we investigated genome-wide DNA methylation in disease-discordant monozygotic twin pairs. This study hypothesized that methylomic biomarkers might facilitate accurate RA detection. A comprehensive series of biomarker detection algorithms were utilized to find t ...[more]
Similar Datasets
Project description:A comprehensive review of optical biosensors for the detection of biomarkers associated with rheumatoid arthritis (RA) is presented here, including microRNAs (miRNAs), C-reactive protein (CRP), rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA), interleukin-6 (IL-6) and histidine, which are biomarkers that enable RA detection and/or monitoring. An overview of the different optical biosensors (based on fluorescence, plasmon resonances, interferometry, surface-enhanced Raman spectroscopy (SERS) among other optical techniques) used to detect these biomarkers is given, describing their performance and main characteristics (limit of detection (LOD) and dynamic range), as well as the connection between the respective biomarker and rheumatoid arthritis. It has been observed that the relationship between the corresponding biomarker and rheumatoid arthritis tends to be obviated most of the time when explaining the mechanism of the optical biosensor, which forces the researcher to look for further information about the biomarker. This review work attempts to establish a clear association between optical sensors and rheumatoid arthritis biomarkers as well as to be an easy-to-use tool for the researchers working in this field.
| S-EPMC7663853 | biostudies-literature
Project description:Rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) are the most frequently used rheumatoid arthritis (RA) diagnostic markers, but they are unable to anticipate the patient's evolution or response to treatment. The aim of this study was to identify possible severity biomarkers to predict an upcoming flare-up or remission period. To address this objective, sera and anticoagulated blood samples were collected from healthy controls (HCs; n = 39) and from early RA (n = 10), flare-up (n = 5), and remission (n = 16) patients. We analyzed leukocyte phenotype markers, regulatory T cells, cell proliferation, and cytokine profiles. Flare-up patients showed increased percentages of cluster of differentiation (CD)3+CD4- lymphocytes (p < 0.01) and granulocytes (p < 0.05) but a decreased natural killer (NK)/T lymphocyte ratio (p < 0.05). Analysis of leukocyte markers by principal component analysis (PCA) and receiver operating characteristic (ROC) curves showed that CD45RO+ (p < 0.0001) and CD45RA+ (p < 0.0001) B lymphocyte expression can discriminate between HCs and early RA patients, while CD3+CD4- lymphocyte percentage (p < 0.0424) and CD45RA+ (p < 0.0424), CD62L+ (p < 0.0284), and CD11a+ (p < 0.0185) B lymphocyte expression can differentiate between flare-up and RA remission subjects. Thus, the combined study of these leukocyte surface markers could have potential as disease severity biomarkers for RA, whose fluctuations could be related to the development of the characteristic pro-inflammatory environment.
| S-EPMC10418816 | biostudies-literature
Project description:Biological products for treatment of rheumatoid arthritis usually are cost effective for healthcare systems in Europe, but they are huge financial burden due to the high number of patients and the significant budget impact. The expected saving from introduction on the market of biosimilars are significant and are linked to better access and affordability. The aim of this study was to conduct comparative price analysis of biological products for rheumatoid arthritis therapy among seventeen EU countries. The point of view is that of the Bulgarian pricing and reimbursement system and the chosen countries are those from external reference basket for prices comparison at manufacturing level. All authorized biological products by EMA with therapeutic indication rheumatoid arthritis were selected. The access for treatment is evaluated as the availability of the product on the market and the prices level. We assessed the availability of all trade names in the price lists of the observed countries. The prices data was obtained from the official web pages of the responsible institutions up to date December 2017. The results show that four out of all six INNs have authorized biosimilars in EMA. Despite its earlier authorization biosimilar adalimumab is not present in any of the price lists of countries. From all eighteen countries only in Lithuania and Estonia there were no published prices of any of the selected medicinal products. Countries with higher number of biosimilar prices are Spain and France. Differences in manufacturers' prices of reference biological products in selected countries in comparison with the lowest manufacturer price are higher with 22 to 69% while the retail prices between 62 and 95%. Differences are mostly notable for rituximab, and less notable for tocilizumab. Manufacturers' and retail prices of biosimilar products were established only for three INNs (etanercept, rituximab, and infliximab). Manufacturers' prices differ between 26 and 75%, while retail prices differ between 40 and 92% for biosimilars. Comparison of the differences between manufacturer prices of reference biological product and biosimilars shows 36% difference for etanercept, 39% for rituximab, and 31% for infliximab, while at retail level the differences are 11, 86, and 143%, respectively. The limitation of the study is that the prices are the official ones without discounts due to confidentiality and the real prices may be lower. The second limitation is that the methodology for pricing differs in the countries and this could also influence the prices on both levels (manufacturer and retail). Introduction of biosimilars on the national markets led to significant decrease in reimbursed prices paid by public funds and thus might benefit the patients' access to biological therapy. The decrease of prices after biosimilars entrance on the market is not as notable as for commodity generics.
| S-EPMC6158404 | biostudies-literature
Project description:Sustained remission is now an achievable goal in rheumatoid arthritis (RA) using modern treat-to-target regimens of disease-modifying anti-rheumatic drugs (DMARDs). Recent studies have demonstrated that up to half of patients in remission can discontinue DMARDs and maintain drug-free remission (DFR), with consequent benefits of avoidance of drug toxicity and the need for regular and expensive safety monitoring. However, there are currently no reliable biomarkers that can predict DFR prior to withdrawal of DMARDs. Aim: As part of a wider study of DMARD withdrawal (the BioRRA study), we aimed to identify predictors of time-to-flare following DMARD cessation using whole-genome bulk RNA sequencing data from circulating CD4+ T cells.
2019-07-12 | GSE122612 | GEO
Project description:Rheumatoid arthritis (RA) causes serious disability and productivity loss, and there is an urgent need for appropriate biomarkers for diagnosis, treatment assessment, and prognosis evaluation. To identify serum markers of RA, we performed mass spectrometry (MS)-based proteomics, and we obtained 24 important markers in normal and RA patient samples using a random forest machine learning model and 11 protein-protein interaction (PPI) network topological analysis methods. Re-analyze markers using additional proteomics datasets, immune infiltration status, tissue specificity, subcellular localization, correlation analysis with disease activity-based diagnostic indications, diagnostic receiver-operating characteristic analysis We discovered that ORM1 in serum is significantly differentially expressed in normal and RA patient samples, which is positively correlated with disease activity, and is closely related to CD56dim natural killer cell, effector memory CD8+ T cell and natural killer cell in the pathological mechanism, which can be better utilized for diagnosis, monitoring disease progression and efficacy assessment. This study supplies a comprehensive strategy for discovering potential serum biomarkers of RA, and provides a different perspective for comprehending the pathological mechanism of RA, identifying potential therapeutic targets, and disease management.
2022-04-19 | PXD032912 | Pride
Project description:The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.
| S-EPMC6827100 | biostudies-literature
Project description:BackgroundCompared to the healthy population, the psychological impact of rheumatoid arthritis(RA) on patients' lives could dramatically lower their oral health-related quality of life (OHRQoL). Our goal is to analyze OHRQoL in RA patients and look into the role of disease activity, dental health index, and Temporomandibular disorders score in maintaining their oral health.MethodsIn a cross-sectional comparative study, we compared a sample of 40 RA patients with 40 age- and gender-matched healthy controls in terms of oral health and OHRQoL. Temporomandibular disorders (TMD), number of decayed, filled, or missing teeth (DMFT), and Oral Health Impact Profile (OHIP) were among the oral health factors studied (OHIP-14). This study also looked at the link between the RA disease activity score (DAS28) and oral health factors.ResultsRA patients had a significantly higher mean (poorer OHRQol) than healthy controls in total oral function, total psychosocial impact, OHIP-14 sum score, OHIP-14 extent score, TMD score and the number of missed teeth (Mann-Whitney U test, P-value < 0.05). After adjustment for DMFT, only the oral function score of OHIP-14 had a significant correlation with disease activity (Mann-Whitney U test, P-value < 0.05). The TMD sum score significantly correlated with disease activity regardless of adjustment for DMFT (Spearman's Correlation test, P-value < 0.05 for both). The number of decayed teeth and missed teeth showed a positive correlation with increased disease activity (Coefficient = 0.239 and 0.245, P-value < 0.05 for both).ConclusionsPatients with RA are less satisfied with their oral health than healthy controls. In RA patients, the number of missing teeth and temporomandibular disorders was substantially greater, and the number of missing teeth and temporomandibular diseases increased significantly with increased disease activity. Although OHRQoL was inversely connected with RA activity, after correcting for decaying, missing, and filled teeth, only the oral function score of OHIP-14 exhibited a slight connection to DAS28.
| S-EPMC9578249 | biostudies-literature
Project description:BackgroundDifferential diagnosis among psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (Abneg RA) can be challenging particularly in the clinical setting of peripheral phenotype and autoantibodies seronegativity. The aim of the study was to identify synovial tissue (ST) biomarkers differentially expressed in PsA and Abneg RA and test their predictive value of therapeutic response.MethodsThirty-four PsA patients [12 DMARD naive and 22 non-responder to methotrexate (MTX-IR)] with peripheral joint involvement and 55 Abneg RA (27 DMARD naive and 28 MTX-IR) underwent US-guided ST biopsy and immunohistochemistry (IHC) for CD68+, CD3+, CD20+, CD21+, CD117+, and CD138+ cells. After study entry, each DMARD-naive patient started MTX therapy and was followed in an outpatient setting for at least 6 months to define the achievement of Minimal Disease Activity (PsA) and DAS remission (Abneg RA) status respectively. Each IR-MTX patient was treated according to EULAR recommendations.ResultsAt study entry, IHC analysis revealed that PsA patients had comparable levels of lining and sublining CD68+ and sublining CD21+, CD20+, and CD3+ cells than Abneg RA, despite the therapeutic regimen. Moreover, regardless of the therapeutic scheme, PsA patients showed higher IHC score of CD117+ cells (p = 0.0004 and p = 0.0005 for naive and MTX-IR patients respectively) compared to Abneg RA patients. Conversely, Abneg RA patients showed higher IHC score of CD138+ cells, irrespective to the therapeutic scheme (p = 0.04 and p = 0.002 for naive and MTX-IR patients respectively). Analyzing the response rate to the therapeutic scheme, naive PsA patients reaching MDA status at 6 months follow-up, showed, at the study entry, lower IHC score of CD3+ cells compared to PsA patients not reaching this outcome (p = 0.02); conversely, naive Abneg RA patients reaching DAS remission status at 6 months follow-up, showed, at the study entry, lower IHC score of sublining CD68+ cells compared to Abneg RA patients not reaching this outcome (p < 0.001).ConclusionsCD117+ and CD138+ cells are differentially distributed among PsA and Abneg RA. Histological analysis of ST may help to solve the clinical overlap between the two diseases and provides prognostic data about the therapy success.
| S-EPMC6509792 | biostudies-literature
Project description:ObjectiveInterstitial lung disease (ILD) is a relatively common extraarticular manifestation of rheumatoid arthritis (RA) that contributes significantly to disease burden and excess mortality. The purpose of this study was to identify peripheral blood markers of RA-associated ILD that can facilitate earlier diagnosis and provide insight regarding the pathogenesis of this potentially devastating disease complication.MethodsPatients with RA who were enrolled in a well-characterized Chinese identification cohort or a US replication cohort were subclassified as having RA-no ILD, RA-mild ILD, or RA-advanced ILD, based on high-resolution computed tomography scans of the chest. Multiplex enzyme-linked immunosorbent assays (ELISAs) and Luminex xMAP technology were used to assess 36 cytokines/chemokines, matrix metalloproteinases (MMPs), and acute-phase proteins in the identification cohort. Unadjusted and adjusted logistic regression models were used to quantify the strength of association between RA-ILD and biomarkers of interest.ResultsMMP-7 and interferon-γ-inducible protein 10 (IP-10)/CXCL10 were identified by multiplex ELISA as potential biomarkers for RA-ILD in 133 RA patients comprising the Chinese identification cohort (50 RA-no ILD, 41 RA-ILD, 42 RA-indeterminate ILD). The findings were confirmed by standard solid-phase sandwich ELISA in the Chinese identification cohort as well as an independent cohort of US patients with RA and different stages of ILD (22 RA-no ILD, 49 RA-ILD, 15 RA-indeterminate ILD), with statistically significant associations in both unadjusted and adjusted logistic regression analyses.ConclusionLevels of MMP-7 and IP-10/CXCL10 are elevated in the serum of RA patients with ILD, whether mild or advanced, supporting their value as pathogenically relevant biomarkers that can contribute to noninvasive detection of this extraarticular disease complication.
| S-EPMC4624107 | biostudies-literature
Project description:BACKGROUND Infliximab shows good efficacy in treating refractory rheumatoid arthritis (RA). However, many patients responded poorly and related studies were inconsistent in predictive biomarkers. This study aimed to identify circulating biomarkers for predicting infliximab response in RA. MATERIAL AND METHODS Public databases of Gene Expression Omnibus (GEO) and ArrayExpress were searched for related microarray datasets, focused on the response to infliximab in RA. All peripheral blood samples were collected before infliximab treatment and gene expression profiles were measured using microarray. Differential genes associated with infliximab efficacy were analyzed. The genes recognized by half of the datasets were regarded as candidate biomarkers and validated by prospective datasets. RESULTS Eight microarray datasets were identified with 374 blood samples of RA patients, among which 191 (51.1%) were diagnosed as non-responders in the subsequent infliximab treatment. Five genes (FKBP1A, FGF12, ANO1, LRRC31, and AKR1D1) were associated with the efficacy and recognized by half of the datasets. The 5-gene model showed a good predictive power in random- and prospective-designed studies, with AUC (area under receiver operating characteristic [ROC] curve)=0.963 and 1.000, and it was also applicable at the early phase of treatment (at week 2) for predicting the response at week 14 (AUC=1.000). In the placebo group, the model failed to predict the response (AUC=0.697), indicating the model's specificity in infliximab treatment. CONCLUSIONS The model of FKBP1A, FGF12, ANO1, LRRC31, and AKR1D1 in peripheral blood is useful for efficiently predicting the response to infliximab treatment in rheumatoid arthritis.
| S-EPMC5404751 | biostudies-literature