Differential expression of IBD susceptibility and IL23R associated pathway genes during ongoing anti-TNF therapy (anti-TNF non-responder vs anti-TNF responder)
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ABSTRACT:
PROVIDER: PRJNA438079 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:IL23R signaling dependent genes are significantly upregulated in Crohn’s disease non-responders compared to responders during ongoing anti-TNF therapy
2018-05-01 | GSE111761 | GEO
Project description:BACKGROUND/RATIONALE:
Treatment outcomes of patients with inflammatory bowel disease (IBD) have improved enormously during the past decade due to the use of anti-tumour necrosis factor (anti-TNF) therapy. As a result, 67 to 91% of paediatric patients and 66% of adult patients is still in sustained remission two years after the initiation of anti-TNF therapy. Prolonged use of anti-TNFs comes with disadvantages such as dose dependent susceptibility to infections and dermatological adverse effects. Preliminary, mostly uncontrolled studies suggest that dose reduction by dosing interval lengthening is a realistic option in a relevant proportion of patients with IBD, provided that intensive follow-up is applied.
OBJECTIVE:
To evaluate whether a faecal calprotectin (FC) guided strategy of anti-TNF dosing interval lengthening is non-inferior in maintaining remission in patients with IBD, compared with an unchanged dosing interval.
| 2359035 | ecrin-mdr-crc
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
Project description:The treatment of auto-inflammatory diseases is often limited by resistance to single cytokine blockade, primarily anti-TNF antibodies. This is a particularly important cause of treatment failure in inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis and is genetically linked to mucosal inflammation by causal variation in its binding sites. However, transcription factors such as T-bet are difficult to target therapeutically. Using CDK9 inhibitors, we show that modulation of P-TEFb (cyclinT1/CDK9), a transcriptional elongation factor downstream of T-bet, potently represses genes responsible for pro-inflammatory signalling, and in particular genes regulated by T-bet. Remarkably, CDK9 inhibition targets genes that are highly expressed in anti-TNF resistant IBD and that predict non-response to anti-TNF therapy. Collectively, our findings reveal CDK9 as a potential target in anti-TNF resistant IBD, which has the potential for rapid translation to the clinic.
2022-06-17 | GSE172372 | GEO
Project description:Anti-TNF (tumor necrosis factor) monoclonal antibodies have revolutionized management of Inflammatory bowel disease. Their common features include high efficacy but also immunogenicity and increased infection risk. Since 2013, two generics or biosimilars of the first anti-TNF have been registered in Europe, which long lerm safety profile needs yet to be established.
This prospective, multicenter, observational cohort study will assess safety of treatment of anti-TNF monoclonal antibodies in inflammatory bowel disease patients in Poland.
Eligible are consecutive patients in whom anti-TNF is started for Crohn’s disease, ulcerative colitis or indeterminate colitis between January 1st, 2014 and December 31st, 2015. Data to be collected include demography, Montreal classification, indication to treatment, previous treatment, operations, extraintestinal manifestations and concomitant diseases. Data on response, tolerability and safety of anti-TNF and on concomitant treatment will be collected. Adverse events logs will be completed. Majority of IBD centres in Poland, pediatric and adult, academic and regional, have agreed to participate in the study.
As a result of the study, the frequency of adverse events in a cohort of Polish IBD patients on various anti-TNFs will be established.
| 2161078 | ecrin-mdr-crc
Project description:Objectives: This study was undertaken to understand the mechanistic basis of response to anti-TNF therapies and determine if transcriptomic changes in the synovium are reflected in peripheral protein markers. Methods: Synovial tissue from 46 RA patients was profiled with RNA sequencing before and 12 weeks after treatment with anti-TNF therapies. Pathway and gene signature analyses were performed on RNA expression profiles of synovial biopsies to identify mechanisms that could discriminate among EULAR good, moderate and non-responders. Serum proteins encoded by synovial genes differentially expressed between EULAR response groups were measured in the same patients. Results: The gene signatures were able to predict good responder patients and pathway analysis identified elevations in immune pathways including chemokine signaling, Th1 and Th2 cell differentiation, and Toll-like receptor signaling uniquely in good responders. These inflammatory pathways were correspondingly down-modulated by anti-TNF therapy only in good responders. Based on cell signature analysis, lymphocyte, myeloid and fibroblast cell populations were elevated in good responders relative to non-responders, consistent with the increased inflammatory pathways. Cell signatures which decreased following anti-TNF treatment were predominately associated with lymphocytes and fewer were associated with myeloid and fibroblast populations. Following anti-TNF treatment and only in good responders, several peripheral inflammatory proteins decreased consistent with corresponding synovial gene changes. Conclusions: Collectively, these data suggest that RA patients with robust responses to anti-TNF therapies are characterized at baseline by immune pathway activation, which decreases following anti-TNF treatment. Understanding mechanisms that define patient responsiveness to anti-TNF may assist in development of predictive markers of patient response and earlier treatment options.
2022-06-06 | GSE198520 | GEO
Project description:Background/aims: Changes in gene expression profiles among individuals with inflammatory bowel diseases (IBDs) could potentially influence the responsiveness to anti-TNF treatment. The aim of this study was to identify genes that could serve as predictors of early response to anti-TNF therapies in pediatric IBD patients prior to the initiation of treatment.Methods: We conducted a prospective, longitudinal, and multicenter study, enrolling 24 pediatric IBD patients aged less than 18 years who were initiating treatment with either infliximab or adalimumab. RNA-seq from blood samples was analyzed using the DESeq2 library by comparing responders and non-responders to anti-TNF drugs. Results: Bioinformatic analyses unveiled 102 differentially expressed genes, with 99 genes exhibiting higher expression in responders compared to non-responders prior to the initiation of anti-TNF therapy. Functional enrichment analyses highlighted defense response to Gram-negative bacteria (FDR =2.3 ×10–7) as the most significant biological processes, and hemoglobin binding (FDR =0.002), as the most significant molecular function. Gene Set Enrichment Analysis (GSEA) revealed notable enrichment in transcriptional misregulation in cancer (FDR =0.016). Notably, 13 genes (CEACAM8, CEACAM6, CILP2, COL17A1, OLFM4, INHBA, LCN2, LTF, MMP8, DEFA4, PRTN3, AZU1, and ELANE) were selected for validation, and a consistent trend of increased expression in responders prior to drug administration was observed for most of these genes, with findings for 4 of them being statistically significant (CEACAM8, LCN2, LTF2, and PRTN3). Conclusions: We identified 102 differentially expressed genes involved in the response to anti-TNF drugs in children with IBDs and validated CEACAM8, LCN2, LTF2, and PRTN3. Genes participating in defense response to Gram-negative bacterium, serine-type endopeptidase activity, and transcriptional misregulation in cancer are good candidates for anticipating the response to anti-TNF drugs in children with IBDs.
2024-02-26 | GSE247146 | GEO
Project description:Expression profiles of anti-TNF responders were compared to profiles of anti-TNF non-responders in order to identify an expression signature for anti-TNF response In total 42 patients were treated with anti-TNF. RNA was isoloated from white blood cells and anti-TNF responders (n=18) were compared to nonresponders (n=24) regarding expression profiles
2012-01-01 | E-GEOD-33377 | biostudies-arrayexpress
Project description:Purpose: IBD diagnosis correlation with failure to achieve corticosteroid-free durable remission upon anti-TNF therapy Results: Enrichment of the GIMATS module (unique cellular signature found in a small cohort of surgically resected iCD ileums by scRNAseq) was also present in early stages of disease, prior to any biological therapy Conclusion: Confirmed the presence of the GIMATS module in bulk expression dataset and revealed that the presence of the module at diagnosis is associated with failure to achieve durable corticosteroid-free remission upon anti-TNF therapy in a pediatric inception cohort
2019-08-21 | GSE134881 | GEO
Project description:Expression profiles of anti-TNF responders were compared to profiles of anti-TNF non-responders in order to identify an expression signature for anti-TNF response
2012-01-01 | GSE33377 | GEO