Gene expression profiling in Abatacept treated Rheumatoid Arthritis patients according to response
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Celine Derambure
PROVIDER: E-GEOD-68215 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The objective of this study was to identify response-specific gene expression fluctuations in methotrexate /abatacept (Aba) treated rheumatoid arthritis patients : responders (R) VS no-responders (NR). Nineteen 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 19 Aba RA patients, 14 were R and 5 were classified as NR. A blood sample was carried out in patients both at baseline (just before the first injection of ABA) and at 6 months in PaxGene tubes.
2020-07-24 | GSE91079 | 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: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:Approximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TNF biologics. In this study, we sought to identify a blood gene expression biomarker correlating with 12-week response to infliximab in patients with moderate to severe disease. Response was assessed using dynamic contrast-enhanced MRI imaging of the wrist. Baseline whole blood samples from 59 patients were collected as part of a placebo-controlled clinical study of infliximab in rheumatoid arthritis. Samples were profiled by Affymetrix microarray and correlation between gene expression and 12-week response was assessed. DAS28 (Disease Activity Score including a 28-joint count)
2014-09-01 | E-GEOD-58795 | biostudies-arrayexpress
Project description:The whole blood was collected pre-treatment from rheumatoid arthritis patients starting the anti_TNF therapy. All patients were naïve to anti_TNFs. The disease activity was measured using the DAS28 score at the pre-treatment visit1 (DAS28_v1) and 14 weeks after treatment visit3 (DAS28_v3). The response to the therapy was evaluated using the EULAR [European League Against Rheumatism] definition of the response. The objective of the data analysis was to identify gene expression coorelating with response as well as to identify genes that differentiate responders versus non-responders pre-treatment. The results of this investigation identified 8 trainscripts that predict responders vs. non-responders with 89% accuracy. Experiment Overall Design: Patients' response to anti-TNF was assessed using EULAR score and patients were classified as responders, moderate responders and non-responders. Genes correlating with the response status have been identified.
2009-09-18 | E-GEOD-15258 | biostudies-arrayexpress
Project description:B cell depletion therapy is efficacious in RA patients failing on TNF blocking agents. However, approximately 40-50% of the rituximab-treated RA patients have a poor response. We investigated wheter baseline gene expression levels can discriminate between clinical nonresponders and responders to rituximab Whole blood total RNA is isolated from PAXgene tubes obtained prior to start of rituximab treatment
2012-04-09 | E-GEOD-37107 | biostudies-arrayexpress
Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens. Total of 28 arrays included in this study, which corresponding to 9 individuals with paired pre/post treatment samples and an additional 10 untreated control individuals. pair_analysis_normData.txt for paired analysis of pre/post treatment; ordinary_analysis_normData.txt for non-paired analysis include all samples, except for 38 Pax V0 and 56 Pax V1, which shows technicial bias and lowest array quality, hence removed from analysis.
2011-08-29 | E-GEOD-31729 | 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:We study the global gene expression profiles of BKV viremia and nephropathy patients using microarrays in order to better understand the immunologic response to polyomavirus BK (BKV). BKV has become increasingly prevalent since the introduction of more potent immunosuppressive agents. It has been shown that as many as 30% of renal transplant recipients develop asymptomatic viral shedding in the urine shortly after transplant, 10-20% have viremia, and as many as 1-10% can go on to develop overt nephropathy (BKVN) that might lead to graft loss. To date, the genomics of BKV viremia and BKVN have not been investigated thoroughly by microarray. Patients who were enrolled in the IRB-approved Immune Monitoring Study had blood PAXGene samples taken at post-transplant visits and had clinically indicated biopsy samples were used for analysis. A total of 17 biopsy samples were used for gene expression profiling microarrays, three with histopathologic diagnosis of BKVN, 3 patients with evidence of BK viral replication in peripheral blood, but normal biopsy and 11 patients with normal biopsies or mild IFTA, and stable graft function. Blood PAXGene samples from 40 patients were used for gene expression profiling by microarrays, 14 patients with stable graft function and without BK viremia, 19 patients' blood samples at the time of BKV viremia, and 7 patients blood samples taken 1-2 months prior to development of BK viremia.
2013-05-23 | E-GEOD-47199 | biostudies-arrayexpress
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