Whole-blood transcriptomic profiling highlights rituximab response in rheumatoid arthritis
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Florent Dumont
PROVIDER: E-GEOD-54629 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
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:Abstract: Analysis of the patterns of gene expression in follicular lymphomas from 24 patients suggested that two groups of tumors might be distinguished. All patients, whose biopsies were obtained before any treatment, were treated with rituximab, a monoclonal antibody directed against the B cell antigen, CD20. Gene expression patterns in the tumors that subsequently failed to respond to rituximab appeared more similar to those of normal lymphoid tissues than to gene expression patterns of tumors from rituximab responders. These findings suggest the possibility that the response of follicular lymphoma to rituximab treatment may be predicted from the gene expression pattern of tumors. This SuperSeries is composed of the SubSeries listed below.
2006-03-07 | GSE4351 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE3646: Follicular lymphoma and normal lymphoid tissue comparisons GSE3647: Follicular lymphoma lymph node Abstract: Analysis of the patterns of gene expression in follicular lymphomas from 24 patients suggested that two groups of tumors might be distinguished. All patients, whose biopsies were obtained before any treatment, were treated with rituximab, a monoclonal antibody directed against the B cell antigen, CD20. Gene expression patterns in the tumors that subsequently failed to respond to rituximab appeared more similar to those of normal lymphoid tissues than to gene expression patterns of tumors from rituximab responders. These findings suggest the possibility that the response of follicular lymphoma to rituximab treatment may be predicted from the gene expression pattern of tumors. Refer to individual Series
2006-03-06 | E-GEOD-4351 | 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: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
2019-09-10 | GSE37107 | GEO
Project description:Rituximab (RTX) is widely used as a first-line therapeutic strategy in B cell-mediated autoimmune diseases. However, a large proportion of patients either do not respond to the treatment or relapse during B cell reconstitution. Primary immune thrombocytopenia (ITP) is a prototypic B cell mediated autoimmune disease in which pathogenic antibodies directed against the platelet membrane glycoprotein IIb-IIIa (GPIIbIIIa) lead to platelet destruction by macrophages in the spleen. In ITP, RTX-mediated B-cell depletion leads to an immediate clinical response in 50% of patients but 80% of patients will subsequently relapse in the next following months. Patients failing to respond or relapsing after RTX treatment are splenectomized when alternative therapies are inefficient or unavailable. Therapeutic splenectomy, resulting in a durable platelet response in 60-70 % of ITP patients, offers a unique access to study the autoimmune response in the spleen. To understand the cellular basis of disease's relapse in secondary lymphoid organs in humans, memory B cells were sorted and analyzed by scRNAseq from the spleen of three different groups of splenectomized ITP patients: 1) Patients that achieved a complete response after a course of RTX and relapsed during B-cell reconstitution (hereafter referred to as “RTX relapse” patients), 2) patients with primary failure of RTX, i.e. who did not respond to treatment at the time of B-cell depletion (“RTX failure” patients), 3) patients with active ITP that were not treated with RTX (“ITP” patients). All were compared with sorted splenic memory B cells from organ donors with no immune disease who died from stroke or head trauma, hereafter referred to as healthy donors (“HD” patients). We also included in this analysis splenic memory B cells from children with sickle cell disease that underwent splenectomy and are known to have a high frequency of B cell activation secondary to classical childhood infections and vaccinations, reflected by an increased number of GC. Single-cell mRNA sequencing was performed according to an adapted version of the SORT-seq protocol (Muraro et al., 2016, Cell Systems 3, 385–394), with cDNA libraries generation, sequencing and reads alignment performed at Single Cell Discoveries (Utrecht, Netherlands).
2021-01-31 | E-MTAB-9955 | biostudies-arrayexpress
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
Project description:Acadesine is a nucleoside analogue with known antileukemic effects in different neoplasms. We investigated the activity of acadesine ne exerts a cytotoxic effect in MCL and synergizes with rituximab supporting clinical examination of this strategy for MCL patients We used microarrays to detail the gene expression changes in acadesine-, rituximab- and combination-treated tumors. Global RNA expression in tumors treated with acadesine, rituximab and the combination in a xenograft model of MCL (Jeko-1). Tumors were collected 18 days after the initiation of the treatments.
2013-06-13 | E-GEOD-47871 | biostudies-arrayexpress
Project description:An autoimmune B cell origin for childhood idiopathic nephrotic syndrome (INS) is predicted based on the efficacy of rituximab (RTX) at maintaining long-term remission from proteinuria. Knowledge regarding the nature of the culprit B cell response is very limited. In particular, no transcriptomics work has been performed to evaluate the B cell response in INS. Here, we performed single-cell RNA-sequencing (scRNAseq) on B cells isolated from peripheral blood mononuclear cells (PBMC) collected from four children with INS during the B cell recovery phase of a previous RTX treamtent while in remission or relapse (paired relapse-remisison samples). We show that the post-RTX B cell landscape is overwhelmingly antigen-inexperienced with minimal transcriptomic differences between relapse and remission. However, post-RTX relapses were associated with an early resurgence of an extrafollicular B cell population expressing genes associated with marginal zone B cells (MZB1, CD24, IGHM, CD1C, TNFRSF13B, GPR183). Together, our study provides evidence for an extrafollicular origin for humoral immunity in active INS.
2023-10-29 | GSE233276 | GEO
Project description:Objective: Rituximab displays therapeutic benefits in the treatment of rheumatoid arthritis (RA) patients resistant to TNF blockade. However, the precise role of B cells in the pathogenesis of RA is still unknown. In this study we investigated the global molecular effects of rituximab in synovial biopsies obtained from anti-TNF resistant RA patients before and after administration of the drug. Methods: Paired synovial biopsies were obtained from the affected knee of anti-TNF resistant RA patients before (T0) and 12 weeks after initiation of rituximab therapy (T12). Total RNA was extracted, labeled according to standard Affymetrix procedures and hybridized on GeneChip HGU133 Plus 2.0 slides. Immunohistochemistry and quantitative real-time PCR experiments were performed to confirm the differential expression of selected transcripts. Results: According to paired Studentâs t-tests, 549 out of 54,675 investigated probe sets were differentially expressed between T0 and T12. Pathway analysis revealed that genes down-regulated between T0 and T12 were significantly enriched in immunoglobulin genes, and genes involved in chemotaxis, leucocyte activation and immune responses (Gene Ontology annotations). By contrast, genes up-regulated between T0 and T12 were significantly enriched in transcripts involved in cell development (Gene Ontology annotation) and wound healing (GSEA). At baseline, higher synovial expression of immunoglobulin genes was associated with response to therapy. Conclusion: Rituximab displays unique effects on global gene expression profiles in synovial tissue of RA patients. These observations open new perspectives in the understanding of the biological effects of the drug and in the selection of patients likely to benefit from this therapy. Twenty patients with RA (17 women and 3 men, average age +/- SEM: 52,6+/-3,8 years) were included in the study. All patients met the American College of Rheumatology classification criteria for the diagnosis of RA. All patients had active disease at the time of tissue sampling and were resistant to TNF blockade. They all had erosive changes imaged on conventional x-rays of the hands and/or feet. All of them had a swollen knee at inclusion. Rituximab therapy was administrated at a dose of 1,000 mg IV at baseline (T0) and at week 2, together with 125 mg IV Methylprednisolone. Clinical parameters at baseline (T0) and 12 weeks after the initiation of therapy (T12) was evaluated using DAS(28)-CRP scores and clinical responses were assessed using EULAR response criteria. Synovial biopsies were obtained by needle-arthroscopy of an affected knee from all patients at T0 and T12. For each procedure, 4 to 8 synovial samples were kept overnight at 4°C in a RNA stabilizing solution (RNALater, Ambion, Applied Biosystems, TX, USA) and then stored at â80°C for later RNA extraction. The same amount of tissue was snap-frozen in liquid nitrogen and kept at â80°C for immunostaining experiments on frozen sections. The remaining material was fixed in 10% formaldehyde and paraffin embedded for conventional optical evaluation and immunostaining of selected markers. All the experiments (RNA extraction, histology, immunohistochemistry) were performed on at least 4 biopsies harvested during every procedure in order to correct for variations related to the potential heterogeneous distribution of synovial inflammation. The study was approved by the ethics committee of the Université catholique de Louvain and informed consent was obtained from all patients. At least 1 µg total RNA could be extracted from 12 paired samples at T0 and T12 for further processing.
2010-10-19 | E-GEOD-24742 | biostudies-arrayexpress