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Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease [RNA-Seq]

ABSTRACT: We investigated the dynamics of gene expression in blood samples of IBD patients treated with infliximab and vedolizumab and analyzed the predictive potential regarding therapy outcome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE191328 | GEO | 2022/07/26

REPOSITORIES: GEO

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Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease [methylation]

Project description:We investigated the dynamics of DNA methylation in blood samples of IBD patients treated with infliximab and analyzed the predictive potential regarding therapy outcome.

2022-07-26 | GSE191297 | GEO

A multi-omics approach to understand and predict therapeutic success of anti-TNF and anti-integrin agents in inflammatory bowel disease

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)

2023-10-31 | E-MTAB-7914 | biostudies-arrayexpress

Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-07-26 | GSE191331 | GEO

Mucosal expression profiling in patients with inflammatory bowel disease before and after first infliximab treatment

Project description:We used microarrays to identify mucosal gene signatures predictive of response to infliximab (IFX) in patients with inflammatory bowel disease (IBD) and to gain more insight into the pathogenesis of IBD. Keywords: drug response and treatment effect Mucosal biopsies were obtained at endoscopy in actively inflamed mucosa from 61 IBD patients (24 ulcerative colitis (UC), 19 Crohnâs colitis (CDc) and 18 Crohnâs ileitis (CDi)), refractory to corticosteroids and/or immunosuppression, before and 4-6 weeks after (except for 1 CDc patient) their first infliximab infusion and in normal mucosa from 12 control patients (6 colon and 6 ileum). The patients were classified for response to infliximab based on endoscopic and histologic findings at 4-6 weeks after first infliximab treatment. Total RNA was isolated from intestinal mucosal biopsies, labelled and hybridized to Affymetrix Human Genome U133 Plus 2.0 Arrays.

2009-11-02 | E-GEOD-16879 | biostudies-arrayexpress

Mucosal expression profiling in patients with inflammatory bowel disease before and after first infliximab treatment

2009-11-03 | GSE16879 | GEO

Whole transcription profile of responders to anti-TNF drugs in pediatric inflammatory bowel disease

Project description:Background: In pediatric inflammatory bowel disease (IBD) up to 30% of patients do not respond to anti-TNF therapy. The aim was to identify pharmacogenomic markers that predict early response to anti-TNF drugs in pediatric patients with IBD. Methods: The study population included 29 responders and 9 non-responders to anti-TNF therapy patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Whole gene expression profiles from total RNA isolated from whole-blood samples of 6 responders and 6 non-responders taken before biologic administration and after 2 weeks were analyzed by RNA next-generation sequencing. The expression of 6 selected genes was measured for validation in all of 38 patients recruited using qPCR; Results: Differentially expressed genes in non-responders versus responders to anti-TNF treatment were identified, 32 prior treatment initiation and 44 after 2 weeks (Log2FC (Fold change)>0.6 o <-0.6 and p value < 0.05). After validation, FCGR1A, FCGR1B and GBP1 were overexpressed in non-responders after 2 weeks of anti-TNF treatment (Log2FC 1.05, 1.21 and 1.08, respectively, p value <0.05,); Conclusion: Expression of the FCGR1A, FCGR1B, and GBP1 genes is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD.

2021-01-14 | GSE159034 | GEO

Therapeutic IL-6 trans-signalling inhibition by olamkicept (sgp130Fc) in patients with active inflammatory bowel disease

Project description:Background A large unmet therapeutic need exists in inflammatory bowel diseases (IBD). Inhibition of interleukin (IL)-6 appears to be effective, but the therapeutic benefit of a complete IL-6/IL-6R blockade is limited by profound immunosuppression. Evidence has emerged, that chronic pro-inflammatory activity of IL-6 is mainly mediated by trans-signalling via a complex of IL-6 bound to soluble IL-6R engaging the gp130 receptor without the need of membrane bound IL6R. We have developed a decoy protein, sgp130Fc, which exclusively blocks IL-6 pro-inflammatory trans-signalling and has shown efficacy in preclinical models of IBD, without signs of immunosuppression. Methods We present a 12-week, open label, prospective phase IIa trial (FUTURE) in 16 patients with active IBD treated with the trans-signalling inhibitor olamkicept (sgp130Fc) to assess molecular mechanisms, safety and effectiveness of IL-6 trans-signalling blockade in vivo. We performed in-depth molecular profiling at various time points before and after therapy induction to identify the mechanism of action of olamkicept. Results Olamkicept was well tolerated and induced clinical response in 44% and clinical remission in 19% of patients. Clinical effectiveness coincided with target inhibition (reduction of phosphorylated STAT3) and marked transcriptional changes in the inflamed mucosa. An olamkicept-specific transcriptional signature, distinguishable from remission signatures of anti-TNF (infliximab) or anti-integrin (vedolizumab) therapies was identified. Conclusion Our data suggest that blockade of IL-6 trans-signaling holds large promise for the therapy of IBD and should undergo full clinical development as a new immunoregulatory therapy of IBD.

2021-04-10 | GSE171770 | GEO

Longitudinal multi-omics reveals subset-specific mechanisms underlying irritable bowel syndrome

Project description:The gut microbiome has been implicated in multiple human chronic gastrointestinal (GI) disorders. Determining its mechanistic role in disease pathogenesis has been difficult due to the apparent disconnect between animal and human studies and a lack of an integrated multi-omics view in the context of disease-specific physiological changes. We integrated longitudinal multi-omics data from the gut microbiome, metabolome, host epigenome and transcriptome in the context of irritable bowel syndrome (IBS) host physiology. We identified IBS subtype-specific and symptom-related variation in microbial composition and function. A subset of identified changes in microbial metabolites correspond to host physiological mechanisms that are relevant to IBS. By integrating multiple data layers, we identified purine metabolism as a novel host-microbial metabolic pathway in IBS with translational potential. Our study highlights the importance of longitudinal sampling and integrating complementary multi-omics data to identify functional mechanisms that can serve as therapeutic targets in a comprehensive treatment strategy for chronic GI diseases.

2020-03-13 | GSE146853 | GEO

The effect of vedolizumab (anti-α4β7-integrin) therapy on colonic mucosal gene expression in patients with ulcerative colitis (UC)

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

A functional genomics predictive network model identifies regulators of inflammatory bowel disease: Mount Sinai Hospital (MSH) Population Specimen Collection and Profiling of Inflammatory Bowel Disease

Project description:This study focuses on inflammatory bowel disease gene expression profiling. Surgical specimens from 134 patients undergoing bowel resection for inflammatory bowel disease (IBD) and non IBD controls at Mount Sinai Medical Center were collected as the source of tissue. Control samples (CLs) were harvested from normal non inflamed bowel located more than 10 cm away from the tumor from patients undergoing bowel resection for sporadic colon cancer. Ulcerative colitis (UC) and Crohn’s (CD) patient samples were all isolated from areas containing moderate to severe inflammation. The diagnostic pathology report for each specimen was provided by the Mount Sinai Hospital Pathology Department. Patients with UC and patients with CD shared common medications including corticosteroids, infliximab, azathioprine, and mesalamine.

2017-07-07 | GSE83687 | GEO

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