Gene expression fluctuation in Abatacept treated Rheumatoid Arthritis patients between baseline and 6 months
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE91079 | GEO | 2020/07/24
REPOSITORIES: GEO
Similar Datasets
Project description:The objective of this study was to identify specific gene expression profiles able to predict the response of rheumatoid arthritis patients treated with methotrexate /abatacept (Aba). Thirty six RA patients were received Abatacept. The drug efficacy was evaluated with the DAS28 score after 6 months of treatment according to the EULAR response criteria. Among 36 Aba RA patients, 17 were responders and 19 were classified as no-responders. A blood sample was carried out in patients just before the first injection of treatment in PaxGene tubes. Two color experiments : patient(Cy5)/Control pool (Cy3).
2017-05-17 | E-GEOD-68215 | biostudies-arrayexpress
Project description:The objective of this study was to identify specific gene expression profiles able to predict the response of rheumatoid arthritis patients treated with methotrexate /abatacept (Aba). Thirty six RA patients were received Abatacept. The drug efficacy was evaluated with the DAS28 score after 6 months of treatment according to the EULAR response criteria. Among 36 Aba RA patients, 17 were responders and 19 were classified as no-responders. A blood sample was carried out in patients just before the first injection of treatment in PaxGene tubes.
2017-05-17 | GSE68215 | GEO
Project description:RA patients (according to ACR/EULAR 2010 criteria) who started abatacept due to high disease activity (DAS28>5.1), were recruited to perform immunological studies at baseline, 3 and 6 months of therapy. Peripheral blood mononuclear cells (PBMCs) were isolated and immune cell populations were characterized using flow cytometry. Proteomic analysis was performed on baseline sera.
2024-01-26 | PXD046112 | Pride
Project description:Our goal was to assess for the histological and transcriptomic effects of Abatacept on RA synovia, and to compare them with previously published data from four other DMARDs: Tocilizumab, Rituximab, Methotrexate and Adalimumab.
2021-08-23 | GSE172188 | GEO
Project description:The efficacy of abatacept in patients with early diffuse systemic sclerosis (dcSSc) was analyzed to test the hypothesis that patients in the inflammatory intrinsic gene expression subset would show the most significant clinical improvement. 84 participants with dcSSc were randomized to receive abatacept or placebo for 12 months. RNA-seq was performed on 233 skin paired biopsies at baseline, 3- and 6-months. Improvement was defined as a 5 point or >20% change in modified Rodnan skin score (mRSS) between baseline and 12 months. Samples were assigned to intrinsic gene expression subset (inflammatory, fibroproliferative, or normal-like). In the abatacept arm, change in mRSS was most pronounced for the inflammatory (p<0.001) and normal-like (p=0.03) subsets relative to placebo. Participants on placebo remained in their molecular subset while inflammatory participants treated with abatacept moved toward normal-like. The CD28 costimulation pathway decreased in patients that improved on abatacept (FDR=5.88x10-4) and was specific to the inflammatory subset (FDR=0%). Patients in the inflammatory subset had elevation of the CD28 costimulation pathway at baseline relative to fibroproliferative (p = 0.0026) and normal-like (p=0.0001) participants. There was a correlation between improved ΔmRSS and baseline expression of the CD28 costimulation pathway (R=-0.62, p=0.02). This study provides an example of precision medicine in SSc clinical trials.
2023-02-01 | GSE217067 | GEO
Project description:Objectives: We monitored the mRNA expression profiles of peripheral blood cells during treatment with a tumor necrosis factor-a inhibitor, infliximab, in patients with rheumatoid arthritis (RA). Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment.Methods: Using a customized low-density cDNA microarray and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the American College of Rheumatology (ACR) response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results: Approximately 15% of the total genes were found to exhibit a greater than 1.5-fold change, compared to their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as interferon-related genes, was strongly correlated with the serum level of C-reactive protein and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders.Conclusions: Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA. Keywords: disease state analysis 18 RA Patients, We have collected blood samples into PAXgene tube systems for microarray measurement from patients as follows, just before first iv-injection of infliximab, 2 weeks, 14 weeks, and 22 weeks after first infliximab injection.
2007-10-09 | E-GEOD-8350 | biostudies-arrayexpress
Project description:Objective: Glucocorticoids (GC) have been a cornerstone of Rheumatoid arthritis (RA)-therapy for the last decades. However, about a third of RA-patients do not respond adequately. As monocytes and T-cells play an important role in RA-pathogenesis, the differential gene expression of these cells before pulse therapy with methylprednisolone was evaluated in order to find predictors for clinical response to GC. Methods: CD14-positive and CD4-positive cells were isolated by MACS sorting from five GC-Responders meeting the European League against Rheumatism (EULAR) response criteria and five Non-Responders. The clinical response was measured by disease activity score (DAS28) at the end of pulse therapy (3x 1000mg Methylprednisolone) at day 5. Cellular RNA was hybridized to Agilent 4x44K microarray chips and differentially expressed genes were calculated by MAANOVA. False discovery rate (FDR) was used as multiple testing correction. Selected genes were verified by quantitative real-time PCR (qPCR). Results: Eight genes were differentially regulated in CD14-cells and 4 genes in CD4-T-cells of GC-Responders compared to Non-Responders. Up-regulation of ERAP2 in monocytes and CD4-cells and LST1 and FAM26F in CD4-Tcells of GC-Responders was verified by qPCR and correlated with DAS28 at day 5 and (for LST1 and FAM26F) with smoking. Conclusion: As ERAP2 and LST1 are implicated in autoimmune disease, their increased expression in GC-Responders before GC-therapy may constitute not only a new tool for prediction of the clinical response to GC in RA, but also warrants further investigation to elucidate their role in the inflammatory process of RA.
2017-11-11 | GSE48823 | GEO
Project description:Objectives: We monitored the mRNA expression profiles of peripheral blood cells during treatment with a tumor necrosis factor-a inhibitor, infliximab, in patients with rheumatoid arthritis (RA). Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment.Methods: Using a customized low-density cDNA microarray and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the American College of Rheumatology (ACR) response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results: Approximately 15% of the total genes were found to exhibit a greater than 1.5-fold change, compared to their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as interferon-related genes, was strongly correlated with the serum level of C-reactive protein and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders.Conclusions: Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA. Keywords: disease state analysis
2007-10-10 | GSE8350 | GEO
Project description:Background and aims
Rheumatoid arthritis (RA) patients are currently treated with biological agents mostly aimed at cytokine blockade such as anti-TNFα therapy. Currently, there are no biomarkers to predict therapy response to these agents. Here, we aimed to predict response to adalimumab (ADA) treatment in RA patients using DNA methylation in peripheral blood
Methods
DNA methylation profiling on whole peripheral blood from 92 RA patients before the start of adalimumab (ADA) was determined using Illumina HumanMethylationEPIC BeadChip Array. After 6 months, treatment response was assessed according to the Alliance of Associations for Rheumatology (EULAR) criteria for disease response. Patients were classified as responders (DAS28<3.2 or decrease of 1.2 points) or as non-responders (DAS28>5.1 or decrease of less than 0.6 points). Machine learning models were built with gradient boosting and stability selection models to predict response prior to ADA treatment with predictor DNA methylation markers.
Results
We demonstrated a 27-feature panel of DNA methylation markers or CpG classifiers that predict response in RA patients treated with ADA. Forty-nine patients were assigned as responder and 43 patients assigned as non-responders. We differentiate responders from non-responders with a high sensitivity (AUC 0.76). The predictor CpGs annotated to genes involved in immunological- and pathophysiological pathways related to RA such as T-cell signaling, B-cell pathology and angiogenesis.
Conclusion
Our findings indicate that DNA methylation signatures discriminate responders and non-responders to ADA treatment and can serve as a tool for therapy prediction.
| EGAS00001007578 | EGA
Project description:The objective of this study was to identify specific gene expression profiles able to predict the response of rheumatoid arthritis patients treated with methotrexate (MTX)/adalimumab (ADA) or MTX/etanercept (ETA). Twenty RA patients were received subcutaneously Adalimumab (40 mg each other week) and eleven RA patients were received Etanercept (50 mg per week). The drug efficacy was evaluated with the DAS28 score after 3 months of treatment according to the EULAR response criteria. A blood sample was carried out in patients just before the first injection of treatment in order to isolate peripheral blood mononuclear cells (PBMC) and extract total RNA.
2024-03-22 | GSE42842 | GEO