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Transcriptome change after tocilizumab therapy in rheumatoid arthritis patients

ABSTRACT: Transcriptome change after tocilizumab therapy in rheumatoid arthritis patients

PROVIDER: PRJNA450318 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7007240.fastq.gz	Fastqsanger.gz
	SRR7007250.fastq.gz	Fastqsanger.gz
	SRR7007241.fastq.gz	Fastqsanger.gz
	SRR7007251.fastq.gz	Fastqsanger.gz
	SRR7007232.fastq.gz	Fastqsanger.gz

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Pharmacogenomics of Rheumatoid Arthritis Therapy

Project description:Pharmacogenomics of Rheumatoid Arthritis Therapy

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Transcriptome change after tocilizumab therapy in rheumatoid arthritis patients

Project description:We compared whole CD4+ and CD8+ T cells from frozen PBMC samples that were collected before and after treatment initiation of each patient with rheumatoid arthritis. Lists consisting of 858 and 950 differentially expressed genes were created from CD4 and CD8, respectively, and these were used for enrichment analysis. As a result, we found that certain pathways were downregulated after TCZ treatment in both CD4+ and CD8+ T cells, including mechanistic target of rapamycin complex 1 (mTORC1) signaling, the IL-2 pathway, and IFN-related genes.

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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.

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Gene Expression Analysis in Peripheral Blood of Patients with Rheumatoid Arthritis

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Gene Expression Analysis in Peripheral Blood of Patients with Rheumatoid Arthritis

Project description:Peripheral blood cells in patients with rheumatoid arthritis before/after IL-6 inhibition The obtained conclusions on the change of each gene expression level before and after MRA medication were as follows. (1) In the case of IL-6, the specific time profile that the expression level dropped at day 21 and increased to some extent at day 42 was observed in 2 of 18 subjects. In other subjects, quite small change or small increase after day 7 was observed. (2) In the case of IL-6R as well as in IL-6, the specific time profile that the expression level dropped at day 21 and increased to some extent at day 42 was observed in 1 of 18 subjects. In other subjects, slow and small increase was observed in 6 of 18. (3) The ratio of mRNA expression level of membrane and soluble type of IL-6R showed marginal difference after tocilizumab treatment, (4) The distinct change of expression level of cytochrome P450 mRNA after tocilizumab treatment was hardly observed in most patients. The measurement of expression level of several genes shown below in peripheral blood of human subjects (18 patients with rheumatic disease) before and after tocilizumab medication using DNA microarray (Hitachi human oligo chip) was conducted in this test, 1) Interleukin 6 (IL-6), membrane IL-6 receptor (IL-6R) and soluble type of the IL-6R, 2) several cytochrome P450 as follows: CYP3A4, CYP2D6, CYP2C9, CYP2C19. Number of human subjects was 18 and peripheral blood samples drawn at 4 time points: day 0 (the first Omeprazole administration was done), day 7 (Tocilizumab administration was done), day 21 and day 42 for each subject were analyzed. On day 0 and day 7, the blood sampling was done before drug administration.

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RNA-Seq of synovial tissue biopsies from individuals with rheumatoid arthritis from the R4RA randomised clinical trial

Project description:Transcriptomic profiles of synovial biopsies of rheumatoid arthritis (RA) patients who were recruited into the R4RA randomised clinical trial. Patients were randomised to treatment with rituximab or tocilizumab. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA and were eligible for treatment with rituximab therapy according to UK NICE guidelines, i.e. failing or intolerant to csDMARD therapy and at least one biologic therapy (excluding trial IMPs) were recruited when fulfilling the trial inclusion/exclusion criteria. For the full study protocol and baseline patient characteristics see Humby et al (2021) The Lancet 397(10271): 305-17. PMID: 33485455.

2022-04-26 | E-MTAB-11611 | biostudies-arrayexpress

Combination of peripheral blood gene expression profiles and clinical parameters predicts response for tocilizumab (anti-IL6) treatment in rheumatoid arthritis

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2011-03-01 | E-GEOD-25160 | biostudies-arrayexpress

Combination of peripheral blood gene expression profiles and clinical parameters predicts response for tocilizumab (anti-IL6) treatment in rheumatoid arthritis

Project description:We used microarrays to identify markers predicting responder status in tocilizumab treatment in rheumatoid arthritis in 13 patients at week 0 and week 4 of treatment.

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Project description:Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disease that is characterized by the presence of inflammatory cytokines, including interleukin-6 (IL-6). Here, we investigated the global molecular effects of Tocilizumab, an approved humanized anti-IL6 Receptor antibody, versus Methotrexate therapy, in synovial biopsy samples collected prospectively in early RA before and 12 weeks after administration of the drug. The results were compared with our previous data, generated in prospective cohorts of Adalimumab- and Rituximab-treated (Methotrexate- and anti-TNF-resistant, respectively) RA patients. We found that Tocilizumab induces a significant down-regulation of genes included in specific pathways: cytokines & chemokines (e.g. IL-6, IL-7, IL-22, CCL8, CCL11, CCL13, CCL19, CCL20), and T cell activation. By contrast, Tocilizumab induces a significant up-regulation of genes associated with healing processes. These effects are significantly more pronounced as compared to Methotrexate, Rituximab, or Adalimumab therapies. By opposition to the effects of Adalimumab, Tocilizumab therapy does not induce a decreased expression of genes involved in cell proliferation. Paired synovial biopsy samples were obtained from the affected knee of early RA patients before and 12 weeks after initiation of Tocilizumab (n=12) or Methotrexate (n=8) therapy. SDAI remission criteria were computed prospectively before, 3 months and 6 months after administration of the drugs and patientsM-bM-^@M-^Y responses were defined according to their SDAI remission status at 6 months. Gene expression studies were performed using GeneChip Human Genome U133 Plus 2.0 arrays.

2013-12-30 | E-GEOD-45867 | biostudies-arrayexpress

Gene expression of monocytes from rheumatoid arthritis patients treated with bDMARDs and methotrexate.

Project description:It is well documented that patients affected by rheumatoid arthritis (RA) have distinct susceptibility to the different biologic Disease-Modifying AntiRheumatic Drugs (bDMARDs) available on the market, probably because of the many facets of the disease. Monocytes are deeply involved in the pathogenesis of RA and we therefore evaluated and compared the transcriptomic profile of monocytes isolated from patients on treatment with methotrexate alone or in combination with tocilizumab, anti-TNFalpha or abatacept, and from healthy donors. Differential expression analysis of whole-genome transcriptomics yielded a list of regulated genes suitable for functional annotation enrichment analysis. Specifically, abatacept, tocilizumab and anti-TNFalpha cohorts were separately compared with methotrexate using a rank-product-based statistical approach, leading to the identification of 78, 6, and 436 differentially expressed genes, respectively.

2023-03-09 | GSE224330 | GEO

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