Transcriptomic profiling predicting response to ustekinumab therapy in patients with Crohn's disease
Ontology highlight
ABSTRACT: This study aimed to identify a biomarker predicting response to ustekinumab therapy. Therefore, we used transcriptomic data (colonic and ileal tissue, CD4 T-cell and CD14 monocytes), which we integrated through Multi-Omics Factor Analysis.
Project description:In this study we wanted to identify baseline predictors of successful anti-TNF and vedolizumab therapy in patients with inflammatory bowel disease (based on tissue transcriptomics and CD4/CD14 transcriptomics)
Project description:In this study we wanted to identify baseline predictors of successful vedolizumab therapy in patients with inflammatory bowel disease.
Project description:Microarray Analysis of Human Whole Blood and Intestinal Biopsy Samples from a Phase 2b, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Ustekinumab in Crohn’s Disease 329 Crohn's biopsies from multiple regions in the intestine of 87 anti TNFa refractory patients and blood samples from 204 patients at Week 0 prior to drug treatment are included in this study
Project description:One of the dysbioses often observed in CD patients is an increased abundance of Escherichia coli (10-100 fold compared to healthy individuals) [Gevers et al., 2014]. E. coli isolates collected from CD and healthy patients were cultivated on LB medium at aerobic conditions up to medium log phase and their total proteomes were analysed by shotgun proteomics by HPLC-MS/MS. Refs. Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W, Ren B, et al. The treatment-naive microbiome in new-onset Crohn’s disease. 2014. Cell Host Microbe 15: 382–92.
Project description:Studying differences in responders and non-responders to therapy in inflammatory bowel disease (IBD) patients (crohn's disease and ulcerative colitis)
Project description:Samples for microarray analysis were derived from terminal ileum and colonic tissues from probands with Crohn's disease and Ulcerative Colitis and control patients, respectively. IBD tissue biopsies from non-inflamed regions 10 cm distant from pathological areas were selected. To minimize inter-individual differences in gene expression and to enrich for IBD-specific transcriptional events, 2.5 µg of total RNA from terminal ileum and colon transversum from four individuals of each patient and control group were used for pooling.
Project description:Patient-derived intestinal organoids provide an excellent tool to unravel mechanisms underlying ulcerative colitis (UC). Fresh biopsies, to isolate crypts and culture organoids, were obtained from both inflamed and non-inflamed regions from eight patients with active UC (Mayo endoscopic subscore ≥2), and from eight non-IBD controls.To address the inflammatory character of ex vivo organoids, we compared the transcriptome of biopsies, crypts and organoids derived from inflamed, and non-inflamed regions and aimed to (re-)induce inflammation ex vivo.
Project description:Altered function of the intestinal epithelium has been considered to play a key role in CD pathogenesis, however exact mechanisms that contribute towards lifelong relapsing mucosal inflammation remain ill defined. DNA methylation (DNAm) is a key epigenetic mechanism known to determine cellular identity by regulating gene transcription with alterations increasingly being implicated in IBD pathogenesis. We generated 312 intestinal epithelial organoids (IEOs) from mucosal stem cells obtained from 168 patients diagnosed with CD, non-IBD/healthy controls and Ulcerative colitis (UC). Genome wide epigenetic profiling of IEOs and primary purified epithelium revealed highly stable, CD associated loss of DNAm in MHC-I related genes which correlated with increased gene expression. Related Single Cell Portal accession number: SCP1884 Related Gene Expression Omnibus accession numbers: GSE57945, GSE75214
Project description:About 5% of celiac disease (CeD) patients do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T-lymphocytes (IELs). RCD type II (RCDII) patients show clonal expansions of IELs that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma.<br>RCDII has a poor prognosis (5-year survival rate <50%) also because of the development of enteropathy-associated T-cell lymphoma. Diagnosis of RCDII is complex and involves a combination of several techniques such as multiplex PCR analysis to determine the clonality of T-cell receptor gene rearrangements and immunohistochemistry or flow-cytometry to define the cell surface markers of IELs. Therefore studying the genetics and genomics of RCD2 susceptibility may provide novel insights into mechanistic basis for RCD2 development. The aim of this experiment was to profile the global gene expression changes in order to understand the dysregulated pathways in RCD2 biopsies and to uncover downstream pathways affected by RCD2 genetic susceptibility loci. <br>All patients were diagnosed with RCD2 and gut biopsies were collected from these patients to perform microarray based gene expression analysis. RNA from eleven RCD2 biopsy samples were analyzed using Illumina Human Ref8 v1 array.