ArticleInflammatory bowel diseases2022
Deleterious Genetic Variation Across the NOD Signaling Pathway Is Associated With Reduced NFKB Signaling Transcription and Upregulation of Alternative Inflammatory Transcripts in Pediatric Inflammatory Bowel Disease.
Article in Inflammatory bowel diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Swimming Upstream: Another Look at NF-κB Inhibition for Colitis Treatment.Digestive diseases and sciences · 2026Article
- Human inflammatory bowel disease-on-a-chip for modelling disease progression, cancer initiation and sex-specific effects.Nature biomedical engineering · 2026Article
- Article
- Inflammatory bowel disease through the lens of microbe-host interactions: immunomodulation, metabolic effects, and genetic susceptibility in microbiota dysbiosis.Frontiers in cellular and infection microbiology · 2026Review
- Distinct colitis-associated macrophages drive NOD2-dependent bacterial sensing and gut homeostasis.The Journal of clinical investigation · 2025Article
- From mitochondria to immune networks: new mesenchymal stem cell strategies to treat periodontitis.Stem cell research & therapy · 2025Review
- Gut Microbiota Serves as a Crucial Independent Biomarker in Inflammatory Bowel Disease (IBD).International journal of molecular sciences · 2025Review
- NOD2 and Crohn's Disease Clinical Practice: From Epidemiology to Diagnosis and Therapy, Rewired.Inflammatory bowel diseases · 2025Review
- Specific deletion of Mettl3 in IECs triggers the development of spontaneous colitis and dysbiosis of T lymphocytes in mice.Clinical and experimental immunology · 2024Article
- Aldehyde dehydrogenase 2-mediated aldehyde metabolism promotes tumor immune evasion by regulating the NOD/VISTA axis.Journal for immunotherapy of cancer · 2023Article
- Recent developments in the assessment and management of inflammatory bowel disease in childhood: a narrative review.Translational pediatrics · 2023Review
- Untargeted metabolomics identifies potential serum biomarkers associated with Crohn's disease.Clinical and experimental medicine · 2023Article
- Prediction of Crohn's Disease Stricturing Phenotype Using a NOD2-derived Genomic Biomarker.Inflammatory bowel diseases · 2023Article
- NOD2 in Crohn's Disease-Unfinished Business.Journal of Crohn's & colitis · 2023Article
- Article
- Evidence of a genetically driven metabolomic signature in actively inflamed Crohn's disease.Scientific reports · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInflammatory bowel disease may arise with inadequate immune response to intestinal bacteria. NOD2 is an established gene in Crohn's disease pathogenesis, with deleterious variation associated with reduced NFKB signaling. We hypothesized that deleterious variation across the NOD2 signaling pathway impacts on transcription.
methodsTreatment-naïve pediatric inflammatory bowel disease patients had ileal biopsies for targeted autoimmune RNA-sequencing and blood for whole exome sequencing collected at diagnostic endoscopy. Utilizing GenePy, a per-individual, per-gene score, genes within the NOD signaling pathway were assigned a quantitative score representing total variant burden. Where multiple genes formed complexes, GenePy scores were summed to create a "complex" score. Normalized transcript expression of 95 genes within this pathway was retrieved. Regression analysis was performed to determine the impact of genomic variation on gene transcription.
resultsThirty-nine patients were included. Limited clustering of patients based on NOD signaling transcripts was related to underlying genomic variation. Patients harboring deleterious variation in NOD2 had reduced NOD2 (β = -0.702, P = 4.3 × 10-5) and increased NFKBIA (β = 0.486, P = .001), reflecting reduced NFKB signal activation. Deleterious variation in the NOD2-RIPK2 complex was associated with increased NLRP3 (β = 0.8, P = 3.1475 × 10-8) and TXN (β = -0.417, P = 8.4 × 10-5) transcription, components of the NLRP3 inflammasome. Deleterious variation in the TAK1-TAB complex resulted in reduced MAPK14 transcription (β = -0.677, P = 1.7 × 10-5), a key signal transduction protein in the NOD2 signaling cascade and increased IFNA1 (β = 0.479, P = .001), indicating reduced transcription of NFKB activators and alternative interferon transcription in these patients.
conclusionsData integration identified perturbation of NOD2 signaling transcription correlated with genomic variation. A hypoimmune NFKB signaling transcription response was observed. Alternative inflammatory pathways were activated and may represent therapeutic targets in specific patients.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.