1107 Gene Expression Profiles Associated with Lack of Response to Intravenous Corticosteroids in Children with Severe Ulcerative Colitis

2009 ◽  
Vol 136 (5) ◽  
pp. A-172
Author(s):  
Boyko Kabakchiev ◽  
Dan Turner ◽  
Jeffrey S. Hyams ◽  
David R. Mack ◽  
Neal S. LeLeiko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Severe Ulcerative Colitis

scholarly journals Expression of Cytokine-Coding Genes BMP8B, LEFTY1 and INSL5 Could Distinguish between Ulcerative Colitis and Crohn’s Disease

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1477
Author(s):  
Daša Jevšinek Skok ◽  
Nina Hauptman ◽  
Miha Jerala ◽  
Nina Zidar
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Experimental Validation ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Gene Expression Profiles ◽  
Cytokine Gene Expression ◽  
Treatment Modalities

Ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by an imbalance between pro-inflammatory and anti-inflammatory cytokines, interfering with the resolution of inflammation. Due to the crucial role of cytokines, new insights into their profiles in UC and CD would help to improve our understanding of pathogenesis and enable the development of new treatment modalities. We provide an expression profile of cytokines in UC and CD, using bioinformatics approach, and experimental validation of expression of the selected genes. We retrieved data and analyzed the cytokine gene expression profiles of UC and CD. From ten genes with inverse expression, common to CD and UC, BMP8B, LEFTY1 and INSL5 were selected for gene expression experimental validation. Experimentally, BMP8B and INSL5 were down-regulated in both CD and UC but followed the bioinformatics trend. The expression of genes LEFTY1 and BMP8B was statistically significant when comparing UC and CD in colon and the expression of gene LEFTY1 showed statistical significance when CD in ileum and colon were compared. Using the bioinformatics approach and experimental validation, we found differences in expression profiles between UC and CD for INSL5, LEFTY1 and BMP8B. These three promising candidate genes need to be further explored at different levels, such as DNA methylation and protein expression, to provide more evidence on their potential diagnostic role in CD and UC.

scholarly journals Transcriptome profiling of ulcerative colitis mouse model suggests biomarkers and therapeutic targets for human colitis

2020 ◽  
Author(s):  
Reza Yarani ◽  
Oana Palasca ◽  
Nadezhda T. Doncheva ◽  
Christian Anthon ◽  
Bartosz Pilecki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Mouse Model ◽  
High Throughput ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Unknown Etiology ◽  
Small Rna Sequencing ◽  
Complex Nature

1.AbstractBACKGROUND & AIMSUlcerative colitis (UC) is an inflammatory bowel disorder with unknown etiology. Given its complex nature, in vivo studies to investigate its pathophysiology is vital. Animal models play an important role in molecular profiling necessary to pinpoint mechanisms that contribute to human disease. Thus, we aim to identify common conserved gene expression signatures and differentially regulated pathways between human UC and a mouse model hereof, which can be used to identify UC patients from healthy individuals and to suggest novel treatment targets and biomarker candidates.METHODSTherefore, we performed high-throughput total and small RNA sequencing to comprehensively characterize the transcriptome landscape of the most widely used UC mouse model, the dextran sodium sulfate (DSS) model. We used this data in conjunction with publicly available human UC transcriptome data to compare gene expression profiles and pathways.RESULTSWe identified differentially regulated protein-coding genes, long non-coding RNAs and microRNAs from colon and blood of UC mice and further characterized the involved pathways and biological processes through which these genes may contribute to disease development and progression. By integrating human and mouse UC datasets, we suggest a set of 51 differentially regulated genes in UC colon and blood that may improve molecular phenotyping, aid in treatment decisions, drug discovery and the design of clinical trials.CONCLUSIONGlobal transcriptome analysis of the DSS-UC mouse model supports its use as an efficient high-throughput tool to discover new targets for therapeutic and diagnostic applications in human UC through identifying relationships between gene expression and disease phenotype.

Mucosal cytokine gene expression profiles as biomarkers of response to infliximab in ulcerative colitis

2012 ◽  
Vol 47 (5) ◽  
pp. 538-547 ◽  
Author(s):  
Renathe Rismo ◽  
Trine Olsen ◽  
Guanglin Cui ◽  
Ingrid Christiansen ◽  
Jon Florholmen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cytokine Gene Expression ◽  
Cytokine Gene

scholarly journals Mucosal microbiota and gene expression are associated with long-term remission after discontinuation of adalimumab in ulcerative colitis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Toshiharu Sakurai ◽  
Hiroki Nishiyama ◽  
Kazuko Sakai ◽  
Marco A. De Velasco ◽  
Tomoyuki Nagai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Expression Profiles ◽  
Bacterial Community Composition ◽  
Gene Expression Profiles ◽  
Significant Shift ◽  
Sustained Remission ◽  
Adalimumab Therapy ◽  
Relapse Group

Abstract Given that sustained remission is the ultimate treatment goal in the management of patients with ulcerative colitis (UC), the decision to stop anti-tumor necrosis factor (anti-TNF) treatment in UC patients is difficult. The aim of this study was to evaluate mucosal microbiota and gene expression profiles associated with long-term remission after discontinuation of anti-TNF therapy. In nine UC patients who received anti-TNF therapy for 6 months, microbiota isolated from uninflamed mucosae and gene expression in inflamed and uninflamed mucosae were investigated at week 0 and at week 24. At treatment initiation, Fusobacterium sp. and Veillonella dispar were over-represented in the relapse group compared with the non-relapse group. After treatment, Dorea sp. and Lachnospira sp. were over-represented in the non-relapse group. In the relapse group only, a significant shift in gut bacterial community composition was found between week 0 and week 24. Gene expression of ALIX (PDCD6IP) and SLC9A3 was significantly higher in the non-relapse group than in the relapse group. Lastly, we used machine learning methods to identify relevant gene signatures associated with sustained remission. Statistical analyses of microbiota and expression profiles revealed differences between UC patients who did or did not keep remission after the discontinuation of TNF inhibitors. Trial registration: UMIN000020785: Evaluation of adalimumab therapy in mesalazine-resistant or -intolerant ulcerative colitis; an observational study (EARLY study).

Response to Anti-α4β7 Blockade in Patients With Ulcerative Colitis Is Associated With Distinct Mucosal Gene Expression Profiles at Baseline

2021 ◽  
Author(s):  
Maria Gazouli ◽  
Nikolas Dovrolis ◽  
Marilena M Bourdakou ◽  
Michalis Gizis ◽  
Georgios Kokkotis ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Immune Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Response To Treatment ◽  
Prognostic Indicators ◽  
Cell Trafficking ◽  
Significant Differential Expression ◽  
Public Data

Abstract Background Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4β7, vedolizumab, in patients with active ulcerative colitis (UC). Methods Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly. Results In the discovery cohort, we identified 21 genes with a statistically significant differential expression between 54-week responders and nonresponders to vedolizumab. Our validation study allowed us to recognize a “core” mucosal profile that was preserved in both discovery and validation cohorts and in the public database. The applied functional annotation and analysis revealed candidate dysregulated pathways in nonresponders to vedolizumab, including immune cell trafficking, TNF receptor superfamily members mediating noncanonical NF-kB pathway, in addition to interleukin signaling, MyD88 signaling, and toll-like receptors (TLRs) cascade. Conclusions Nonresponse to vedolizumab in UC is associated with specific pretreatment gene-expression mucosal signatures and dysregulation of particular immunological and inflammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.

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