The DNA methylation Profile of Undifferentiated Arthritis Patients Anticipates their Subsequent Differentiation to Rheumatoid Arthritis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE175364 | GEO | 2021/06/16
REPOSITORIES: GEO
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Project description:Rheumatoid arthritis (RA) is an inflammatory joint disorder that results in progressive joint damage when insufficiently treated. In order to prevent joint destruction and functional disability in RA, early diagnosis and initiation of appropriate treatment with Disease-Modifying Antirheumatic Drugs (DMARDs) is needed. However, in daily clinical practice, patients may initially display symptoms of arthritis that do not fulfil the classification criteria for a definite diagnosis of RA, or any other joint disease, a situation called “Undifferentiated Arthritis” (UA). Out of the patients with UA, 30 to 50% usually develop RA, and early identification of these remains a challenge. At the present time, although several risk factors associated with the development of RA have been identified (6-9), a model that reliably predicts the probability of evolution of UA into RA in individual patients is lacking. In order to better identify early RA patients, an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) collaboration recently developed new classification criteria. Although these criteria are more sensitive, the risk of over-diagnosis is an important issue to consider, especially in very early disease. In this context, the present study explores the feasibility of a molecular diagnosis of arthritis, based on the identification of disease-specific transcriptomic profiles in synovial biopsies from patients with arthritis according to the underlying condition. In a previous study, we performed global analyses of gene expression in synovial biopsies from patients with RA, Systemic Lupus Erythematosus (SLE) and Osteoarthritis (OA), using high-density oligonucleotide spotted microarrays. We found that the gene expression profiles are strikingly different according to the underlying condition. Thus, the majority of the genes up-regulated in SLE are type I Interferon-inducible genes, as compared with the up-regulation genes involved in T cell and B cell activation in RA, and in extracellular matrix homeostasis in OA. Based on these results, similar analyses were performed in synovial biopsies from patients with seronegative arthritis (SA) and microcrystalline arthritis (MIC), in order to identify disease-specific molecular signatures.
2012-03-27 | GSE36700 | GEO
Project description:The identification of predictive markers in an early undifferentiated arthritis (UA) patients is pivotal for selecting appropriate therapies to avoid a poor prognosis. In this work, we investigated the association between clinical features and DNA methylation patterns in monocytes from UA patients to seek potential prognostic biomarkers.
2022-05-25 | GSE189426 | GEO
Project description:An exploration of the peripheral blood CD4+ T-cell transcriptome of early arthritis clinic attendees, seeking novel diagnostic tools and pathophysiological insights. Ex-vivo CD4+ T-cell RNA was obtained following first early arthritis clinic attendance from 173 patients. Four diagnostic categories were confirmed at median 28 months follow-up. Outcome categories are ACPA- RA (A; n=31), ACPA+ RA (B; n=41), Non-RA Inflammatory arthritis (C; n=56), and Non-RA/Non-Inflammatory arthritis (D; n=45). In order to derive and validate a diagnostic gene signature, samples were split into Training set (where patients could be diagnosed at presentation; n=111) and validation set of undifferentiated arthritis (UA; n=62) patients, in whom diagnosis could only be confirmed after the follow-up period. Arrays were processed in two phases (phases 1 and 2). Phase 1 was split into 4 labelling batches, Phase 2 was split into 2 labelling batches. Batch effects were controlled for using this information using the empirical Bayes approach of Johnson et al. (2007). The supplementary file 'GSE20098_non-normalized.txt' contains non-normalized data for Samples GSM502124-GSM502280 and GSM506251-GSM506266.
2012-03-03 | E-GEOD-20098 | biostudies-arrayexpress
Project description:In osteoarthritis (OA) and rheumatoid arthritis (RA), many pathological alterations result from aberrant macrophage hyperactivation in the inflamed synovial membrane, and inhibition of macrophage effector functions is a therapeutic strategy in both diseases. Little is known, about the specific genetic circuits that are differentially deregulated in RA and OA macrophages. microRNA (miR) are short single stranded non-coding RNAs involved in the post-transcriptional regulation of gene expression. Altered expression of miRs has been described under various pathological conditions, including rheumatic and other autoimmune diseases. Here we compared the miR expression profile in macrophages isolated from OA and RA patients miR expression in OA and RA macrophages was analyzed using Exiqon miRCURY microarrays. Three biological replicates (patients) were analyzed. Two samples (RA vs OA) were hybridized per microarray.
2016-02-05 | E-GEOD-63745 | biostudies-arrayexpress
Project description:In osteoarthritis (OA) and rheumatoid arthritis (RA), many pathological alterations result from aberrant macrophage hyperactivation in the inflamed synovial membrane, and inhibition of macrophage effector functions is a therapeutic strategy in both diseases. Little is known, about the specific genetic circuits that are differentially deregulated in RA and OA macrophages. microRNA (miR) are short single stranded non-coding RNAs involved in the post-transcriptional regulation of gene expression. Altered expression of miRs has been described under various pathological conditions, including rheumatic and other autoimmune diseases. Here we compared the miR expression profile in macrophages isolated from OA and RA patients
2016-02-05 | GSE63745 | GEO
Project description:In Rheumatoid Arthritis, restoration of immune self-tolerance represents an unmet therapeutic need, since a significant proportion of RA patients show inadequate clinical response. Based on the previously described tolerogenic phenotype of pDCs in RA responding to anti-TNF agents, we aimed to explore the molecular mechanisms involved in the tolerogenic reprogramming of pDCs in RA.
2022-07-31 | E-MTAB-11933 | biostudies-arrayexpress
Project description:Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by synovitis and, bone and cartilage destruction. Although disease-modifying anti-rheumatic drugs (DMARDs) have dramatically improved clinical outcomes, these therapies are not universally effective in all patients due to the heterogeneity of RA pathogenesis. Therefore, there is still a need to elucidate molecular mechanisms underlying RA pathogenesis to identify novel therapeutic targets. In this study, we identified Budding uninhibited by benzimidazoles 1 (BUB1) was highly expressed in RA patients’ synovium and murine ankle tissue with arthritis. Since we revealed CD45+CD11b+ myeloid cells as Bub1 highly expressing population among synovial cells, myeloid cell-specific Bub1 conditional knockout (cKO) mice were generated. Obtained cKO mice showed no significant phenotypes in healthy conditions while they exhibited reduced bone mineral density under K/BxN serum-transfer arthritis. Moreover, histomorphometric analysis suggested that the reduced bone mass was caused by increased osteoclast differentiation and activation. RNA-seq and subsequent Gene set enrichment analysis (GSEA) demonstrated significantly enriched NF-κB pathway among up-regulated genes in RANKL-stimulated bone marrow macrophages obtained from Bub1 cKO, suggesting Bub1 KO macrophages are sensitive to inflammatory conditions. Indeed, osteoclastogenesis in Bub1 KO macrophages was enhanced by RANKL and TNFα treatment and localization of NF-κB component p65 was observed. Finally, osteoclastogenesis was increased by Bub1 inhibitor BAY1816032 treatment. These data suggested that BUB1 in myeloid cells plays a protective role against bone loss under inflammatory arthritis.
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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) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors. Keywords: disease state analysis
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