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Genomic responses of mouse synovial fibroblasts during TNF-driven arthritogenesis greatly mimic those of human rheumatoid arthritis

ABSTRACT: Genomic responses of mouse synovial fibroblasts during TNF-driven arthritogenesis greatly mimic those of human rheumatoid arthritis

PROVIDER: PRJNA376508 | ENA |

REPOSITORIES: ENA

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Synovial inflammatory pathways characterize anti-TNF-responsive rheumatoid arthritis patients

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

Genomic responses of mouse synovial fibroblasts during TNF-driven arthritogenesis greatly mimic those of human rheumatoid arthritis

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-04-19 | GSE95256 | GEO

Genomic responses of mouse synovial fibroblasts during TNF-driven arthritogenesis greatly mimic those of human rheumatoid arthritis (H3K4me3-Seq).

Project description:We used deep sequencing to probe the transcriptome, the methylome and the chromatin landscape of cultured mouse arthritogenic SFs at three stages of disease, as well as SFs stimulated with human TNF. We performed bioinformatics analyses at the gene, pathway and network levels, compared mouse and human data, and validated selected genes in both species.

2017-04-19 | GSE95254 | GEO

Genomic responses of mouse synovial fibroblasts during TNF-driven arthritogenesis greatly mimic those of human rheumatoid arthritis (MethylCap-Seq).

2017-04-19 | GSE95252 | GEO

Genomic responses of mouse synovial fibroblasts during TNF-driven arthritogenesis greatly mimic those of human rheumatoid arthritis (RNA-Seq).

2017-04-19 | GSE95251 | GEO

Expression data from rheumatoid arthritis synovial macrophages

Project description:Macrophages from RA synovial fluids were compared to primary human monocyte-derived macrophages.

2017-08-10 | GSE97779 | GEO

Gene expression in rheumatoid arthritis synovial macrophages

Project description:Macrophages from RA synovial fluids were compared to primary human blood-derived macrophages. Keywords: disease state analysis

2008-02-14 | GSE10500 | GEO

Expression data from Rheumatoid Arthritis synovial tissue samples

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

Synovial fluid proteome in rheumatoid arthritis

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

Microarray analysis of the synovial membrane of rheumatoid arthritis patients undergoing anti-TNF therapy

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

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