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PROVIDER: PRJNA158433 | ENA |
REPOSITORIES: ENA
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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:New and effective therapeutical options are available for the treatment of Rheumatoid Arthritis. One of such treatments is rituximab, and chimeric anti-CD20 antibody that selectively depletes the CD20+ B cell subpopulation. Similar to established anti-TNF alpha therapies, there is a subgroup of RA patients that do not experience significant clinical response. Therefore, one of the major necessities in actual RA therapeutical management is to identify reliable predictors of the response to this therapies. In the present study we have evaluated 3 blood cell types (i.e. whole blood, isolated B cells and isolated CD4 T cells) using microarray gene expression profiling to identify their potential use as biomarkers for rituximab response. In all three tissues evaluated, we have identified statistically significant differentially expressed genes. The most relevant candidates have been reevaluated using RealTime PCR. These genes were: TRAF1 and arginase 1 in whole blood, Toll-Like Receptor 4 (TLR4) in CD4+ T cells and AT-rich interactive domain 3A (ARID3A) in B cells. In the present study we have demonstrated the potential of different blood cell types for the prediction of the response to rituximab. In particular, we have found a set of relevant candidate genes that could be the basis for future treatment response prediction.
2009-10-02 | GSE15316 | GEO
Project description:Objective: We performed whole-blood transcriptomic profiling for patients with rheumatoid arthritis (RA) who received rituximab (RTX). We aimed to identify a molecular signature that could predict the clinical response to RTX and transcriptomic changes after RTX therapy.
2015-01-01 | GSE54629 | GEO
Project description:Objective: We performed whole-blood transcriptomic profiling for patients with rheumatoid arthritis (RA) who received rituximab (RTX). We aimed to identify a molecular signature that could predict the clinical response to RTX and transcriptomic changes after RTX therapy. Methods: We performed a microarray assay of the whole human genome with RNA from a peripheral blood sample taken before the first RTX cycle from 68 patients included in the SMART study (24 EULAR non-responders and 44 responders at week 24). The transcriptomic profile was also assessed 24 weeks after the first RTX administration
2015-01-01 | E-GEOD-54629 | biostudies-arrayexpress
Project description:Whole-blood transcriptomic profiling highlights rituximab response in rheumatoid arthritis
| PRJNA237237 | ENA
Project description:Endogenous or iatrogenic antitumor immune responses can improve the course of follicular lymphoma (FL), but may be diminished by immunoregulatory mechanisms in the tumor microenvironment. These may include effects of programmed death (PD)-1, a coinhibitory receptor that impairs T-cell function and is highly expressed on intratumoral T cells. In a Phase II trial, we tested the efficacy of pidilizumab, a humanized anti-PD-1 monoclonal antibody, with rituximab in patients with rituximab-sensitive FL relapsed after 1-4 prior therapies. Pidilizumab was administered at 3 mg/kg every 4 weeks for 4 infusions, plus 8 optional infusions every 4 weeks for patients with stable disease or better. Starting 2 weeks after the first infusion of pidilizumab, rituximab was given at 375 mg/m2 weekly for 4 weeks. Peripheral blood and tumor biopsies were studied to assess immunological effects of pidilizumab. The combination was well-tolerated, with no grade 3/4 toxicities. Overall (66%) and complete (52%) response rates in 29 evaluable patients were high, with tumor regression in 86% of patients. Median progression-free survival was 18.8 months, and was not reached for the 19 responders. Peripheral blood immunophenotyping showed increased memory CD4+ T cells and activation of NK cells after pidilizumab therapy. Tumor response and progression-free survival were associated with T-cell activation gene signatures in tumor gene expression profiling data, both at baseline and in changes induced by pidilizumab. The efficacy of pidilizumab with rituximab compared favorably to historical retreatment with rituximab monotherapy in patients with relapsed FL. Pidilizumab may benefit patients with pre-existing endogenous antitumor immune responses. This set contains 26 samples in total. 8 pairs of pre- and post-treatment samples, and 10 additional pre-treatment samples.
2013-11-21 | E-GEOD-52562 | biostudies-arrayexpress
Project description:Interferon beta (IFN-β) is a first line treatment for patients with relapsing forms of MS, but response to the drug varies and to date there are no biomarkers associated with individual patient response. Whole blood gene expression data from a clinical study of patients initiating treatment with intramuscular IFN-β1a (Avonex®) was comprehensively analyzed for gene signatures distinguishing between good vs. poor responders where the latter were defined by increases in number and size of observed lesions in quantitative imaging over a 6-month period. We observed signatures related to B-cell activation in subject gene expression prior to treatment while T-cell and interleukin signatures were observed in the same subjects immediately after treatment. These signatures form a basis for developing predictors of IFN-β1a response in patients both prior to and after IFN-β1 treatment.
2019-04-11 | GSE113006 | GEO
Project description:Interferon beta (IFN-β) is a first line treatment for patients with relapsing forms of MS, but response to the drug varies and to date there are no biomarkers associated with individual patient response. Whole blood gene expression data from a clinical study of patients initiating treatment with intramuscular IFN-β1a (Avonex®) was comprehensively analyzed for gene signatures distinguishing between good vs. poor responders where the latter were defined by increases in number and size of observed lesions in quantitative imaging over a 6-month period. We observed signatures related to B-cell activation in subject gene expression prior to treatment while T-cell and interleukin signatures were observed in the same subjects immediately after treatment. These signatures form a basis for developing predictors of IFN-β1a response in patients both prior to and after IFN-β1 treatment.
2019-04-11 | GSE113004 | GEO
Project description:Systemic sclerosis (SSc) shows complex clinical manifestations including progressive skin and internal organ fibrosis. SSc can be divided into 'intrinsic subsets' by gene expression suggesting patient-specific heterogeneity in pathogenesis or temporal evolution of disease. Here we validate these subsets using an independent patient population, and test whether the genes vary over time with patients changing subsets as disease progresses, or if the genes are a stable feature of the patients within each subset. Skin biopsies were analyzed from 13 dSSc patients enrolled in an open label study of rituximab, 9 dSSc patients not treated with rituximab, and 9 healthy controls. These data recapitulate the patient 'intrinsic subsets' described previously with gene expression associated with cell proliferation, inflammatory processes, and a normal-like group. Serial skin biopsies showed consistent and non-progressing gene expression. We were unable to detect significant differences in gene expression before and after rituximab treatment, consistent with an apparent lack of clinical response. Serial biopsies from each patient stayed within the same gene expression subset regardless of treatment regimen or the time point at which they were taken. This demonstrates the intrinsic subsets are an inherent, reproducible and stable feature of SSc that is independent of disease duration. Skin biopsies were analyzed from 13 dSSc patients enrolled in an open label study of rituximab, 9 dSSc patients not treated with rituximab, and 9 healthy controls.
2012-03-23 | E-GEOD-32413 | biostudies-arrayexpress
Project description:Purpose: Accurate prediction of clinical response is the prerequisite for individualized therapy in chronic lymphocytic leukemia (CLL). We hypothesized that sequential assessment of gene expression changes early during therapy may well reflect behaviour of the leukemic clone in response to specific drugs. Patients and Methods: Gene expression profiles (GEP) were determined in CD19+ selected B-cells from 20 patients treated with fludarabine and cyclophosphamide (FC) (N=10) or FC plus rituximab (FCR) (N=10). Samples were collected in the first cycle before and within 48hours after initiation of treatment. GEP analysis was stratified by clinical response 3 months after start of therapy. Results: GEP before treatment detected high expression of 34 genes correlated with response and 32 genes correlated with resistance to therapy. These genes were related to regulation of apoptosis, cell cycle, cell adhesion, and signal transduction. Different results were obtained with sequential GEP: Sixteen genes were up-regulated after rituximab infusion in non-responders. Rituximab therapy resulted in down-regulation of AKT1 indicating involvement of the PI3-kinase pathway in CD20-signaling. Up-regulation of 24 genes after FC (including ITPKB (inositol 1,4,5-trisphosphate 3-kinase) and CD44) and of 36 genes after FCR (including CD49d) was associated with resistance. Down-regulation of CTLA4 correlated with poor response to FC. CD44, CD49d and the PI3-kinase signaling pathway were confirmed as potential therapeutic targets to overcome resistance by (protein analysis) or functional experiments. Conclusion Sequential GEP provides rapid and relevant information for prediction of response and resistance. This approach could be used to guide and adapt individualized therapy in CLL. 50 Samples from CD19 selected B-cells, three treatments (rituximab, FC and RFC), 10 replicates for each treatment, 20 replicates for control condition
2011-03-01 | E-GEOD-15490 | biostudies-arrayexpress