Similar Datasets
Project description:Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, driven by mucosal immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin monoclonal antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed a single-cell and spatial transcriptomic and proteomic analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with UC on VDZ or other therapies. We identified significant effects of VDZ on mononuclear phagocyte (MNP) subsets, in addition to modest effects on lymphocyte populations. Spatial transcriptomics and proteomics of formalin-fixed, paraffin-embedded (FFPE) biopsies at single-cell resolution demonstrated trends towards increased abundance and proximity of activated MNP and fibroblast subsets in active colitis compared to HC, with inhibition by VDZ. Spatial transcriptomics of archived FFPE specimens pre-treatment identified epithelial-, MNP-, and fibroblast-enriched genes related to VDZ response versus non-response, and these were validated in an external, publicly accessible bulk transcriptomic dataset. Single cell and spatial multi-omics highlight important roles for myeloid, stromal, and epithelial subsets in UC.
2024-01-22 | GSE250490 | GEO
Project description:Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, driven by mucosal immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin monoclonal antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed a single-cell and spatial transcriptomic and proteomic analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with UC on VDZ or other therapies. We identified significant effects of VDZ on mononuclear phagocyte (MNP) subsets, in addition to modest effects on lymphocyte populations. Spatial transcriptomics and proteomics of formalin-fixed, paraffin-embedded (FFPE) biopsies at single-cell resolution demonstrated trends towards increased abundance and proximity of activated MNP and fibroblast subsets in active colitis compared to HC, with inhibition by VDZ. Spatial transcriptomics of archived FFPE specimens pre-treatment identified epithelial-, MNP-, and fibroblast-enriched genes related to VDZ response versus non-response, and these were validated in an external, publicly accessible bulk transcriptomic dataset. Single cell and spatial multi-omics highlight important roles for myeloid, stromal, and epithelial subsets in UC.
2024-01-22 | GSE250488 | GEO
Project description:Ulcerative colitis (UC) is a chronic inflammatory condition of the colon, driven by mucosal immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin monoclonal antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we performed a single-cell and spatial transcriptomic and proteomic analysis of peripheral blood and colonic biopsies in healthy controls (HC) and patients with UC on VDZ or other therapies. We identified significant effects of VDZ on mononuclear phagocyte (MNP) subsets, in addition to modest effects on lymphocyte populations. Spatial transcriptomics and proteomics of formalin-fixed, paraffin-embedded (FFPE) biopsies at single-cell resolution demonstrated trends towards increased abundance and proximity of activated MNP and fibroblast subsets in active colitis compared to HC, with inhibition by VDZ. Spatial transcriptomics of archived FFPE specimens pre-treatment identified epithelial-, MNP-, and fibroblast-enriched genes related to VDZ response versus non-response, and these were validated in an external, publicly accessible bulk transcriptomic dataset. Single cell and spatial multi-omics highlight important roles for myeloid, stromal, and epithelial subsets in UC.
2024-01-22 | GSE250487 | GEO
Project description:Ulcerative colitis (UC) is driven by disruptions in host-microbiota homoeostasis, but current treatments exclusively target host inflammatory pathways. To understand how host-microbiota interactions become disrupted in UC, we collected and analysed six faecal- or serum-based omic datasets (metaproteomic, metabolomic, metagenomic, metapeptidomic and amplicon sequencing profiles of faecal samples and proteomic profiles of serum samples) from 40 UC patients at a single inflammatory bowel disease centre, as well as various clinical, endoscopic and histologic measures of disease activity. A validation cohort of 210 samples (73 UC, 117 Crohn's disease, 20 healthy controls) was collected and analysed separately and independently. Data integration across both cohorts showed that a subset of the clinically active UC patients had an overabundance of proteases that originated from the bacterium Bacteroides vulgatus. To test whether B. vulgatus proteases contribute to UC disease activity, we first profiled B. vulgatus proteases found in patients and bacterial cultures. Use of a broad-spectrum protease inhibitor improved B. vulgatus-induced barrier dysfunction in vitro, and prevented colitis in B. vulgatus monocolonized, IL10-deficient mice. Furthermore, transplantation of faeces from UC patients with a high abundance of B. vulgatus proteases into germfree mice induced colitis dependent on protease activity. These results, stemming from a multi-omics approach, improve understanding of functional microbiota alterations that drive UC and provide a resource for identifying other pathways that could be inhibited as a strategy to treat this disease.
| S-EPMC8852248 | biostudies-literature
Project description:Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) worldwide. Better understanding of the pathogenesis of UC has led to the development of novel therapeutic agents that target specific mediators of the inflammatory cascade. A number of biological agents have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of UC and several more are currently in various phases of drug development. The commonly used agents include TNF? antagonists (e.g. infliximab, adalimumab, and golimumab) and anti-integrin agents (vedolizumab). These biological agents have profoundly influenced the management of UC patients, especially those with refractory disease. This paper reviews the currently available knowledge and evidence for the use of various biological agents in the treatment of UC.
| S-EPMC4423460 | biostudies-literature
Project description:Adult inflammatory bowel disease is incompletely understood. We combine unbiased single-cell RNA sequencing (gene expression profiling, CITE-seq derived cell surface protein data, TCR and BCR sequence data) with unbiased spatial transcriptomics to interrogate changes across immune and non-immune populations in colitis and health, across tissue and blood. We compare idiopathic ulcerative colitis with hitherto under-studied immune checkpoint therapy induced colitis, utilizing non-inflamed disease states as additional controls. We identify patterns of inflammation and response unique and common to both diseases, and infer changes in cell trafficking with potential therapeutic implications. We go on to localize disease-specific changes in tissue using spatial transcriptomics, leveraging this data to interrogate cellular interactions in an unbiased manner, allowing us to describe novel microdomains of inflammation and repair.
2024-04-12 | GSE189184 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2024-04-12 | GSE189185 | GEO
Project description:Ulcerative colitis (UC) and Crohn's disease (CD) are chronic, relapsing inflammatory bowel diseases associated with significant morbidity. Conventional therapies for these diseases include corticosteroids, aminosalicylates, immunomodulators, and monoclonal antibodies. Over the years tumor necrosis factor (TNF)-α antagonists alone or in combination with other therapies have emerged as the cornerstone of treatment for induction and maintenance of remission of moderate to severe UC and CD. Unfortunately, some patients with moderate to severe UC and CD are unable to attain or maintain remission with TNF-α antagonist treatment. Vedolizumab, a humanized monoclonal antibody, is the first integrin receptor antagonist approved that selectively antagonizes α4β7 gastrointestinal integrin receptors. US Food and Drug Administration approval is for treatment of patients with moderate to severe active UC and CD who have inadequate response with, lost response to, or are intolerant to a TNF-α antagonist or an immunomodulator; or have inadequate response with, are intolerant to, or demonstrate dependence on corticosteroids. When administered according to approved dosing in patients with moderate to severe CD and UC, vedolizumab induces clinical response rates up to 31.4% and 47.1% at week 6, and clinical remission rates up to 39% and 41.8% at week 52, respectively. Serious adverse events reported with vedolizumab include serious infections, malignancies, and anaphylaxis. Since vedolizumab is gastrointestinal selective, to date, it has not shown evidence of causing progressive multifocal leukoencephalopathy; however, postmarketing studies monitoring for this adverse effect are ongoing. Further assessment of vedolizumab earlier in the course of these diseases and in combination with other therapies is warranted.
| S-EPMC4549690 | biostudies-literature
Project description:Ixekizumab is a selective monoclonal antibody targeting interleukin-17A, approved for the treatment of chronic plaque psoriasis. It has rarely been associated with inflammatory bowel disease (IBD) in randomized trials only. We report a unique case of severe new-onset ulcerative colitis in a young male complicated by cytomegalovirus infection who was on ixekizumab therapy for plaque psoriasis. We recommend that clinicians should exercise caution before prescribing ixekizumab as it seems to induce and exacerbate IBD.
| S-EPMC6244035 | biostudies-other
Project description:Microarrays were used to investigate the the effect of vedolizumab (VDZ) therapy on colonic mucosal gene expression in UC patients and compared the changes to those observed with infliximab (IFX) therapy.
2016-10-11 | GSE73661 | GEO