Project description:In the current study, we compared DNA methylation patterns using the Illumina 850k array technology between normal synovial fibroblasts and synovial fibroblasts from early (veRASF) and late stages of RA (estRASF) and transient, resolving arthritis (rSF). In doing so, we obtained a detailed view of changes in DNA methylation that occur during the development of RA from the earliest clinically apparent stages to established RA with its typical signs and symptoms.
Project description:In the current study, we compared DNA methylation patterns using the Illumina 450k array technology between normal synovial fibroblasts and synovial fibroblasts from early (veRASF) and late stages of RA (estRASF) and transient, resolving arthritis (rSF). In doing so, we obtained a detailed view of changes in DNA methylation that occur during the development of RA from the earliest clinically apparent stages to established RA with its typical signs and symptoms.
Project description:Object: to understand Infliximab treatment effect on the molecular expression of tissue at disease site 4mm punch biopsies were performed on involved and uninvolved skin at baseline in 5 Ps patients. A repeat biopsy was performed at week 2 after IFX therapy at a site adjacent to the baseline biopsy of involved skin. Synovial biopsies were performed on the knee of 3 RA and 3 PsA paired-subjects with a Parker Pearson biopsy needle (Dyna Medical, London, Canada) under ultrasound guidance at baseline and repeated on the same knee at week 10
Project description:All the synovial tissue specimens for TMT relative quantitative proteomics and further experiments were obtained from the patients with RA or OA undergoing surgical joint replacement at the clinical of joint surgery (Xi'an Hong Hui Hospital, Xi'an Jiaotong University, China). The diagnosis of the patients were accorded to the criteria of the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) in 2010.a quantitative proteomic profiling of synovial tissue obtained from RA and OA patients was carried out by using TMT labeling followed by high resolution mass spectrometry analysis. We have identified 4822 proteins out of which 510 proteins were found to be differentially expressed by ≥1.2 fold change in the synovial tissue from RA verses OA patients.
Project description:We explored transcriptomic profiles of paired synovial biopsies from RA patients, in order to assess heterogeneity in synovial tissue at the individual level. Pairwise comparison of transcriptomic profiles showed similar expression of RA-related molecular pathways (TCR signaling, T cell co-stimulation and response to TNF⍺), thereby showing that global molecular alterations in RA synovitis are similar between small and large joints from the same patient.
Project description:<p>Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p>
Project description:Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 vaccine recipient controls for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.
Project description:MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states, including inflammatory autoimmune diseases. By using high-throughput microRNA profiling analysis, we identified a series of miRNAs dysregulated in local inflammatory lesions of human patients with autoimmune diseases such as RA. We isolated the synovial tissues from four RA patients as well as from two normal people (victims of accidental injury) and two osteoarthristis (OA) patients as controls for comparison. Total RNA was extracted for the TaqManM-BM-. Low Density Assay v3.0
Project description:TNF antagonists are routinely used in severe rheumatoid arthritis (RA) patients who failed conventional DMARD therapy. According to large clinical trials, the three available drugs (adalimumab, infliximab and etanercept) display similar effects in terms of efficacy, tolerability and side effects. These studies also indicate that about 25% of RA patients treated with TNF-antagonists do not display any significant clinical improvement. The aim of this study was to investigate global molecular patterns in synovial biopsies from RA patients obtained 12 weeks after initiation of adalimumab therapy. All patients had rheumatoid arthritis (RA), according to the American College of rheumatology criteria for the diagnosis of RA. They had active disease at the time of initiation of adalimumab therapy and were resistant to conventional therapy. They all had erosive changes imaged on conventional x-rays of the hands and/or feet. All patients were treated with disease-modifying antirheumatic drugs (DMARD’s), 23 with methotrexate (median dose 15 mg/week, range 7.5 – 20 mg/week), and 2 with leflunomide (20 mg/day); 18 of them were treated with low-dose steroids (prednisolone ≤ 7.5 mg/day). Six patients had been included in double-blind clinical trials before inclusion in the present study (1 in a Golimumab versus placebo trial, 3 in a MapKinase inhibitor versus placebo trial and 2 in a TACE-inhibitor versus placebo trial). These trials were stopped at least 3 months prior to initiation of TNF-blocking therapy. All drug dosages were stable from at least 3 months prior to initiation of TNF blocking therapy until completion of the study. No steroid injections were allowed during the duration of the study. Adalimumab therapy was initiated at a dosage of 40 mg subcutaneously every other week. Disease activity at baseline and 12 weeks after initiation of therapy (T12) was evaluated using DAS(28)-CRP (3- and 4-variables) scores, and response to therapy was assessed according to the EULAR response criteria that categorize patients in responders (good- or moderate-) and non- (or poor-) responders based on changes in DAS activity between T0 and T12 and absolute DAS values at T12. Synovial biopsies were obtained by needle-arthroscopy of knee of the patients at T12. The aim of the study was to compare gene expression profiles in synovial tissue of RA patients who responded versus not responded to adalimumab therapy.