ArticleGastroenterology2018
Clinical and Genomic Correlates of Neutrophil Reactive Oxygen Species Production in Pediatric Patients With Crohn's Disease.
Article in Gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Comprehensive evaluation of clinical phenotypes and pathogenic features in late-onset monogenic inflammatory bowel disease: a comparative study with infantile-onset cases.BMC gastroenterology · 2025Pooled it
- Preventing Colitis-Associated Colon Cancer With Antioxidants: A Systematic Review.Cellular and molecular gastroenterology and hepatology · 2021Pooled it
- Article
- Large-scale analysis of temporal gene expression variation in peripheral blood.Nature communications · 2026Article
- Monogenic forms of inflammatory bowel disease: Genetic mechanisms, models, and clinical implications.Molecular medicine (Cambridge, Mass.) · 2026Review
- Interpretable inflammation landscape of circulating immune cells.Nature medicine · 2026Article
- Integrated multi-omics profiling of the early post-infarct heart reveals a hub gene network associated with myeloid-driven inflammation.Frontiers in cardiovascular medicine · 2026Article
- Association Between Perioperative Inflammatory Trajectories and Postoperative Hirschsprung-Associated Enterocolitis: Insights from Group-Based Trajectory Modeling.Journal of inflammation research · 2026Article
- Eosinophil-derived COX-2 protects against experimental colitis through the PGEbioRxiv : the preprint server for biology · 2025Article
- Towards IBD Prediction and Prevention: The Contribution of Genetics and Genomics.Inflammatory bowel diseases · 2025Review
- Neutrophils and NETs in Pathophysiology and Treatment of Inflammatory Bowel Disease.International journal of molecular sciences · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Host-pathobiont interactions in Crohn's disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Article
- Neutrophil-to-Lymphocyte Ratio at Diagnosis Predicts Colonoscopic Activity in Pediatric Inflammatory Bowel Diseases.Clinical and translational gastroenterology · 2025Article
- Neutrophils: From Inflammatory Bowel Disease to Colitis-Associated Colorectal Cancer.Journal of inflammation research · 2025Review
- Exploring Potential Causal Links: How Parkinson's Disease Brain Damage Impacts Liver Health-A Mendelian Randomization and Transcriptomic Study.Journal of inflammation research · 2025Article
- Article
- Dual role of CD177 + neutrophils in inflammatory bowel disease: a review.Journal of translational medicine · 2024Review
- Investigating the molecular mechanisms underlying the co-occurrence of Parkinson's disease and inflammatory bowel disease through the integration of multiple datasets.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
34 authors at 15 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsIndividuals with monogenic disorders of phagocyte function develop chronic colitis that resembles Crohn's disease (CD). We tested for associations between mutations in genes encoding reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, neutrophil function, and phenotypes of CD in pediatric patients.
methodsWe performed whole-exome sequence analysis to identify mutations in genes encoding NADPH oxidases (such as CYBA, CYBB, NCF1, NCF2, NCF4, RAC1, and RAC2) using DNA from 543 pediatric patients with inflammatory bowel diseases. Blood samples were collected from an additional 129 pediatric patients with CD and 26 children without IBD (controls); we performed assays for neutrophil activation, reactive oxygen species (ROS) production, and bacteria uptake and killing. Whole-exome sequence analysis was performed using DNA from 46 of the children with CD to examine associations with NADPH gene mutations; RNA sequence analyses were performed using blood cells from 46 children with CD to test for variations in neutrophil gene expression associated with ROS production.
resultsWe identified 26 missense mutations in CYBA, CYBB, NCF1, NCF2, and NCF4. Patients with CD who carried mutations in these genes were 3-fold more likely to have perianal disease (P = .0008) and stricturing complications (P = .002) than children with CD without these mutations. Among patients with CD with none of these mutations, 9% had undergone abdominal surgery; among patients with mutations in these NADPH oxidase genes, 31% had undergone abdominal surgery (P = .0004). A higher proportion of neutrophils from children with CD had low ROS production (47%) than from controls (15%) among the 129 patients tested for ROS (P = .002). Minor alleles of the NADPH genes were detected in 7% of children with CD whose neutrophils produced normal levels of ROS vs 38% of children whose neutrophils produced low levels of ROS (P = .009). Neutrophils that produced low levels of ROS had specific alterations in genes that regulate glucose metabolism and antimicrobial responses.
conclusionsWe identified missense mutations in genes that encode NADPH oxidases in children with CD; these were associated with a more aggressive disease course and reduced ROS production by neutrophils from the patients.
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