Synovial inflammatory pathways characterize anti-TNF-responsive rheumatoid arthritis patients
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ABSTRACT:
PROVIDER: PRJNA815686 | ENA |
REPOSITORIES: ENA
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Project description:Objectives: This study was undertaken to understand the mechanistic basis of response to anti-TNF therapies and determine if transcriptomic changes in the synovium are reflected in peripheral protein markers. Methods: Synovial tissue from 46 RA patients was profiled with RNA sequencing before and 12 weeks after treatment with anti-TNF therapies. Pathway and gene signature analyses were performed on RNA expression profiles of synovial biopsies to identify mechanisms that could discriminate among EULAR good, moderate and non-responders. Serum proteins encoded by synovial genes differentially expressed between EULAR response groups were measured in the same patients. Results: The gene signatures were able to predict good responder patients and pathway analysis identified elevations in immune pathways including chemokine signaling, Th1 and Th2 cell differentiation, and Toll-like receptor signaling uniquely in good responders. These inflammatory pathways were correspondingly down-modulated by anti-TNF therapy only in good responders. Based on cell signature analysis, lymphocyte, myeloid and fibroblast cell populations were elevated in good responders relative to non-responders, consistent with the increased inflammatory pathways. Cell signatures which decreased following anti-TNF treatment were predominately associated with lymphocytes and fewer were associated with myeloid and fibroblast populations. Following anti-TNF treatment and only in good responders, several peripheral inflammatory proteins decreased consistent with corresponding synovial gene changes. Conclusions: Collectively, these data suggest that RA patients with robust responses to anti-TNF therapies are characterized at baseline by immune pathway activation, which decreases following anti-TNF treatment. Understanding mechanisms that define patient responsiveness to anti-TNF may assist in development of predictive markers of patient response and earlier treatment options.
2022-06-06 | GSE198520 | GEO
Project description:Synovial biopsies of Rheumatoid Arthritis patients were obtained at week 20 of anti-TNF therapy. The clinical response to therapy was determined comparing the DAS28 at this time point with the baseline DAS28, using the EULAR response criteria. Gene expression profiles of patients responding to anti-TNF therapy were compared to non-responders and different genes, pathways and deconvoluted cell types were found to be differential between both groups of rheumatoid arthritis patients.
2020-06-30 | GSE140036 | GEO
Project description:Synovial biopsies of Rheumatoid Arthritis patients with active disease were obtained prior to anti-TNF therapy. Clinical response to anti-TNF treatment was measured 20 weeks later using the EULAR response criteria. Gene expression profiles of patients responding to anti-TNF therapy were compared to non-responders and several genes were found to be differentially expressed between both groups of Rheumatoid Arthritis patients.
2019-07-26 | GSE47726 | GEO
Project description:Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Microarray analysis of 83 synovial samples provides insight into the expression-level differences between patients at the site of disease activity. Synovial samples from Rheumatoid Arthritis patients were obtained during joint resection and profiled using microarrays.
2014-04-22 | E-GEOD-48780 | biostudies-arrayexpress
Project description:OBJECTIVE: MicroRNAs (miRNAs, miRs), a class of small non-coding RNA molecules, are posttranscriptional regulators involved in a plethora of cellular functions and have been proposed as potential therapeutic targets in various diseases, including rheumatoid arthritis (RA). In this study, we sought to discover novel miR associations in synovial fibroblasts (SFs), a key cell type mediating RA pathogenesis, by performing miR expression profiling on cells isolated from the human TNF transgenic mouse model (TghuTNF or Tg197). METHODS: miR expression in SFs isolated from 8-week-old, fully diseased TghuTNF and WT littermate control mice were determined by deep sequencing of small RNAs and the arthritic profile was established by pairwise comparisons of the two groups. qRT-PCR analysis was utilised for profile validation purposes and miR quantitation in patient SFs. Dysregulated miR target genes and pathways were predicted via bioinformatic algorithms. Synovial Fibroblasts isolated from TghuTNF mice (2 x biological replicates) and control WT littermate mice (2 x biological replicates)
2012-05-13 | E-GEOD-31667 | biostudies-arrayexpress
Project description:In 15 patients with rheumatoid arthritis the baseline expression (t=0) of type I IFN-regulated genes was determined in peripheral blood cells (PAXgene) using cDNA-microarrays and compared to levels one month after (t=1) anti-TNF treatment (infliximab). Therefore, we used 43K cDNA microarrays from the Stanford Functional Genomics Facility (http://microarray.org/sfgf/) printed on aminosilane-coated slides containing ~20.000 unique genes. Only one batch of arrays was used for all experiments. First DNA spots were UV-cross linked to the slide using 150-300 mJoules. Sample preparation and microarray hybridization were performed as described previously (1,2). Data storage and filtering was performed using the Stanford Microarray Database (http://genome-www5.stanford.edu//) as described previously. 1. van der Pouw Kraan TC, Wijbrandts CA, van Baarsen LG, Voskuyl AE, Rustenburg F, Baggen JM et al.: Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients. Ann Rheum Dis 2007, 66: 1008-1014. 2. van der Pouw Kraan TC, van Baarsen LG, Rustenburg F, Baltus B, Fero M, Verweij CL: Gene expression profiling in rheumatology. Methods Mol Med 2007, 136: 305-327. Abbreviations: - Bnrs are the different patients analyzed - PAX or Paxgene indicates the total RNA was isolated from peripheral blood obtained in PAXgene tubes - CRS: common reference sample: We made a common reference that consisted of a mixture of mRNAs isolated from 11 different cell lines (Perou CM, Jeffrey SS, van de RM et al. Distinctive gene expression patterns in human mammary epithelial cells and breast cancers. Proc Natl Acad Sci U S A. 1999; 96:9212-9217) supplemented with RNA from rheumatoid synovial tissue, fibroblasts, and activated peripheral blood mononuclear cells (PBMCs). - PMT: photomultiplier tube: the sensitivity/intensity of the scanner can be adjusted to prevent spot saturation. Compound Based Treatment: anti-TNF (infliximab) reference_design
2010-06-24 | E-GEOD-19821 | biostudies-arrayexpress
Project description:Rheumatoid arthritis (RA) is a chronic autoinflammatory disorder that affects small joints. Despite intense efforts, there isno definitive marker yet for early diagnosis RA and for monitoring the progression of this disease. We sought to catalog the proteins present in the synovial fluid of patients with rheumatoid arthritis. To identify lower abundance proteins, we undertook two approaches – we depleted the abundant proteins using a multiple affinity removal system (MARS14) column and we enriched glycoproteins using a lectin affinity column. The peptides were analyzed by LC-MS/MS on a high resolution Fourier transform mass spectrometer.
2016-06-13 | PXD000740 | Pride
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
2004-11-04 | GSE1919 | GEO
Project description:Rheumatoid arthritis (RA) is a complex and clinically heterogeneous autoimmune disease. Microarray analysis of 83 synovial samples provides insight into the expression-level differences between patients at the site of disease activity.
2014-04-22 | GSE48780 | GEO
Project description:Inflammatory tissues are characterized by low oxigen concentrations (hypoxia). These conditions are very different from that usually present in tissue cultures where transcriptomic profiles of human fibroblasts from inflammatory tissues have been previously analysed. The aim of this study was to characterize the changes on gene expression induced by hypoxia in human synovial fibroblasts. We used microarray expression profiling in paired normoxic and hypoxic cultures of healthy and rheumatoid arthritis (RA) synovial fibroblasts (HSF and RASF). Hypoxia induces significant changes on the expression of large groups of genes in both HSF and RASF. The hypoxic and normoxic profiles are also different between both groups. These data demonstrate that hypoxia induces significant changes on gene expression in HSF and RASF and identify differences between RASF and HSF. Synovial fibroblasts obtained from 6 patients with rheumatoid arthritis (RASF) and 6 sex and age matched adult healthy donors (HSF) were used. SF cultures were incubated for 22 hours under normoxic or hypoxic (0.5% O2) conditions. Nine experiments per group were performed, single experiments with three SF lines, and duplicated in other three lines per group. All 18 normoxia-hypoxia experiments (36 microarray data) were used for paired analysis of the changes induced by hypoxia in HSF or RASF.
2010-12-10 | E-GEOD-21959 | biostudies-arrayexpress