Transcriptomic profiling of peripheral blood mononuclear cells from rheumatoid arthritis patients before tofacitinib treatment
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Homo sapiens
SUBMITTER: Fangyi Lu
PROVIDER: E-MTAB-16533 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Background: Results obtained from our previous study using a label-free quantitation (LF) proteomic approach in which dynamic range compression was used to profile lower abundance proteins, demonstrated few proteins that were differentially abundant within the synovial fluid (SF) when comparing Autologous Chondrocyte Implantation (ACI) responders and non-responders at baseline (1). This study builds upon our previous findings by assessing higher abundance proteins within these SFs; providing a more global proteome analysis from which we can understand more fully the biology underlying ACI success or failure. Methods: Isobaric tagging for relative and absolute quantitation (iTRAQ) proteomics was used to assess SFs from ACI responders (mean Lysholm improvement of 33; n=14) and non-responders (mean Lysholm decrease of 14; n=13) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Differentially abundant proteins were investigated using pathway analyses and the iTRAQ proteomic dataset was combined with our published proteomic dataset of dynamically compressed SFs, from which an interactome network model of systemic protein interactions was generated. Results: iTRAQ proteomics has confirmed our previous finding that there is a marked proteome shift in response to cartilage harvest (70 and 54 proteins demonstrating ≥2.0 fold change between Stages I and II in responders and non-responders, respectively) and has highlighted 28 proteins that were differentially abundant between responders and non-responders to ACI, that were not found in the LF study; 16 of which were altered at baseline. Two protein abundance changes (Complement C1S subcomponent and Matrix metalloproteinase 3 (MMP3), have been biochemically validated. Combination of the iTRAQ and LF proteomic datasets has generated in-depth SF proteome information that has been used to generate interactome networks representing ACI success or failure, from which functional pathways that are dysregulated in ACI non-responders have been identified. Conclusions: Several candidate biomarkers for baseline prediction of ACI outcome have been identified. A holistic overview of the SF proteome in responders and non-responders to ACI has been profiled providing a better understanding of the biological pathways underlying clinical outcome, particularly the differential response to cartilage harvest in non-responders.
2018-05-03 | PXD008321 | Pride
Project description:Immune cells are majorly dysregulated in rheumatoid arthritis patients and are a major cause of pathogenesis and progression of this autoimmune condition. As mitochondria are master regulators of metabolism of all cells present in human body, it is of prime importance to study mitochondrial homeostasis in immune cells for identifying any dysfunction contributing to pathogenesis or progression of RA. The objective of our study is to understand the mitochondrial and mitochondrially driven alterations in immune cells of RA patients which may cause them to perform abnormal functions and may have an important contribution in progression of the disease.
2020-06-22 | PXD011934 | Pride
Project description:Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with localized bone involvement characterized by the presence of bone erosions. Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion. Thirty-nine premenopausal RA patients and 20 healthy age-matched women were recruited for this study. Classical monocytes were isolated from peripheral blood through negative selection. Sequencing library was constructed using the Quant-seq® 30 mRNA-Seq Library Prep Kit (Lexogen®) and sequenced using an Illumina Seq 2500 platform (Illumina®). Differential expression analysis was performed between patients and control groups. Therefore, gene sets analysis was performed to identify the enriched biological pathways. Results suggested that alterations in pathways related to the inflammatory process and impairment of bone formation have an important role in the pathophysiology of bone erosions in patients with rheumatoid arthritis.
2023-09-19 | E-MTAB-13361 | biostudies-arrayexpress
Project description:The aim of the study is to identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients. DNA from baseline peripheral blood mononuclear cells was extracted from treatment naive RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy (deltaDAS28) over the first 3 months in 69 RA patients.
2021-02-07 | E-MTAB-10159 | biostudies-arrayexpress
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.
2009-04-15 | E-GEOD-15602 | biostudies-arrayexpress
Project description:In this study we performed RNA-seq to identify human transcriptomic signatures associated with antibody responses to an oral cholera vaccine. We isolated total RNA from peripheral blood mononuclear cells of vaccinated volunteers who following two priming oral immunisations, had either strong or no antibody responses to the antigen components of the cholera vaccine. We performed a longitudinal and comparative PBMC transcriptional assessment of high vs low antibody vaccine responders at day 0, 19 and 44 post vaccination. We also identified unique and overlapping genes of low and high vaccine responders 0, 19 and 44 post vaccination. Due to General Data Protection Regulation (GDPR) access to human sequenced raw data is restricted and will be made available upon request through https://doi.org/10.17044/scilifelab.12213434
2021-03-23 | E-MTAB-9069 | biostudies-arrayexpress
Project description:[Aim] To characterize the transcriptomic changes in skin lesions of lepromatous leprosy patients before and after multidrug therapy (MDT). Likewise, not all patients improve their bacillary index after MDT. Thus, the further analysis aims to compare patients who responded or did not to MDT and identify underlying modulated genes. [Design] Lepromatous patients were treated for 12 months with multidrug therapy. Skin biopsy samples were collected before (BT) and after treatment (AT). At the end of 12 months of MDT, those who decreased their bacillary index by at least one log10 unit were considered responders (R) and otherwise non-responders (NR). RNA was isolated, poly-A captured, and sequenced. Comparisons both within-patient and between-patients were done. [Results] At the end of MDT, genes involved with lipid metabolism, innate and adaptive immunity, extracellular matrix, and epidermis development were all differentially expressed. Comparisons between responders and non-responders to MDT identified differentially expressed genes involved with lipid metabolism, semaphorin-plexin signaling pathway, epidermis development, and vasculogenesis. This study identified gene expression signatures modulated after 12 months of MDT. Also, a subset of patients with poor bacterial clearance has dysregulated pathways relative to responders.
2022-04-10 | E-MTAB-11605 | biostudies-arrayexpress
Project description:We tested the role of distinct STM populations in the modulation of synovial tissue environment in ex vivo STM-FLS micro co-cultures. We first FACS-sorted total synovial tissue fibroblasts as we described previously from biopsies of RA patients. FLS were seeded at 3000/well alone or in contact with either 3000/well FACS-sorted MerTK/CD206neg or MerTK/CD206pos STMs from patients with active or remission RA respectively for 48h. The modulatory effect on the FLS was evaluated by comparing their expression of 446 immune/stromal genes (scRNAseq BD Rhapsody) 32,141 FLS were evaluated. FLS cells cultured alone exhibited 4 distinct activation states: FLS cluster 1 (FLS1) expressed extracellular matrix proteins (e.g. COL1A1, COL1A2) and TGFb (TGFBI, TGFB3); FLS2 expressed cell adhesion molecules (e.g. ITGB2, SELPLG); FLS3 expressed receptors for TGFb and resolvin (e.g.CMKLR1 and TGFBR1); and FLS4 expressed high levels of glycolytic enzymes and proliferation markers (e.g. LDHA, PGK1, ENO1 and PCNA). Interestingly, upon co-culture with MerTK/CD206neg an additional fifth cluster (FLS5) emerged with inflammatory properties In contrast to inflammatory effect of the MerTK/CD206neg STMs on FLS, the MerTK/CD206pos population, especially that isolated from biopsies of RA patients in sustained disease remission, induced repair response of FLS as manifested by increased expression of collagens (e.g. COL1A) and TGFb response genes (e.g. TGFBI) Importantly, MerTK/CD206neg and MerTK/CD206pos STMs isolated from the biopsies of the same patient (either with active RA or RA in remission) elicited these divergent FLS responses. These suggest that these two distinct STM populations play opposing role in synovium (pro-inflammatory versus protective).
2020-04-18 | E-MTAB-8873 | biostudies-arrayexpress
Project description:In recent years, a circulating subset of B cells phenotypically negative for CD21 has been reported to be expanded in chronic infectious and autoimmune inflammatory diseases. While reports on the function of these cells differ by disease origin, their role in rheumatoid arthritis (RA) has remained elusive. Here, we combine clinical data with flow cytometric analyses for patients untreated for and newly diagnosed with RA. We show correlations between the frequency of CD21-Tbet+CD11c+ and destruction of both cartilage and bone in in the joints of patients at the time of diagnosis. Combining single-cell 5’ RNA sequencing with B-cell receptor (VDJ)-enriched sequencing, we are able to identify the Tbet+CD11c+ cells in the scRNA-seq data from untreated newly diagnosed RA patients. Further, we describe a characteristic gene expression pattern, with overrepresentation of upregulated genes involved in antigen processing and presenting processes. The same gene signature is near identically expressed by autoimmune-associated cells infiltrating synovial tissue of RA patients. Our findings suggest that Tbet+CD11c+ B cells may be poised for antigen presentation in the periphery, and could be capable of recirculating between the periphery and joint tissue, thereby promoting autoimmune responses. Overall, we demonstrate a potential pathogenic role of Tbet+CD11c+ B cells in RA, in which they contribute to joint destruction.
2025-12-31 | E-MTAB-11961 | biostudies-arrayexpress
Project description:Polyarticular Juvenile Idiopathic Arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial roleof monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity. Seventeen healthy subjects and eighteen premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level. We identified 440 DEGs in pJIA patients of which 360 were up-regulated and 80 down-regulated. GSEA highlighted TNF- and IFN- response. Importantly, this analysis detected genes targeted by pJIA therapy, but also identified new modulators of immuno-inflammation. PLAUR, IL1B, IL6, CDKN1A, PIM1 and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels. These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine.
2024-05-06 | E-MTAB-14035 | biostudies-arrayexpress