ArticleThe American journal of clinical nutrition2024
Multiplexed immunohistochemical evaluation of small bowel inflammatory and epithelial parameters in environmental enteric dysfunction.
Article in The American journal of clinical nutrition, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Structural and Hormonal Changes Associated With Starvation in Zambian Adult Patients With Esophageal Strictures: A Cross-Sectional Study.Health science reports · 2026Article
- Host-microbiome determinants of ready-to-use supplemental food efficacy in acute childhood malnutrition.JCI insight · 2025Article
- Mild Duodenal Mucosal Injury and Increased Type I Interferon Signaling Are Preludes to Celiac Disease.Laboratory investigation; a journal of technical methods and pathology · 2025Article
- Duodenal transcriptomics demonstrates signatures of tissue inflammation and immune cell infiltration in children with environmental enteric dysfunction across global centers.The American journal of clinical nutrition · 2024Article
- Duodenal quantitative mucosal morphometry in children with environmental enteric dysfunction: a cross-sectional multicountry analysis.The American journal of clinical nutrition · 2024Article
- Biomarker relationships with small bowel histopathology among malnourished children with environmental enteric dysfunction in a multicountry cohort study.The American journal of clinical nutrition · 2024Article
- Histopathology underlying environmental enteric dysfunction in a cohort study of undernourished children in Bangladesh, Pakistan, and Zambia compared with United States children.The American journal of clinical nutrition · 2024Article
- The Environmental Enteric Dysfunction Biopsy Initiative (EEDBI) Consortium: mucosal investigations of environmental enteric dysfunction.The American journal of clinical nutrition · 2024Article
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19 authors.
Funding
Abstract
backgroundEnvironmental enteric dysfunction (EED) is characterized by reduced absorptive capacity and barrier function of the small intestine, leading to poor ponderal and linear childhood growth.
objectivesTo further define gene expression patterns that are associated with EED to uncover new pathophysiology of this disorder.
methodsDuodenal biopsies from cohorts of children with EED from Bangladesh, Pakistan and Zambia were analyzed by immunohistochemistry (IHC) to interrogate gene products that distinguished differentiation and various biochemical pathways in immune and epithelial cells, some identified by prior bulk RNA sequence analyses. Immunohistochemical staining was digitally quantified from scanned images and compared to cohorts of North American children with celiac disease (gluten-sensitive enteropathy) or with no known enteric disease and no pathologic abnormality (NPA) detected in their clinical biopsies.
resultsAfter multivariable statistical analysis, we identified statistically significant (P < 0.05, 2-tailed t-test) elevated signals representing cluster of differentiation 45 (80%; 95% confidence interval [CI]: 24%, 127%), lipocalin 2 (659%; 95% CI: 198%, 1838%), and regenerating family 1 beta (221%; 95% CI: 47%, 600%) and lower signals corresponding to granzyme B (-74%; 95% CI: -82%, -62%), and sucrase isomaltase (-58%; 95% CI: -75%, -29%) in EED biopsies compared with NPA biopsies. Computerized algorithms also detected statistically significant elevation in intraepithelial lymphocytes (49%; 95% CI: 9%, 105%) and proliferation of leukocytes (267%; 95% CI: 92%, 601%) in EED biopsies compared with NPA biopsies.
conclusionsOur results support a model of chronic epithelial stress that decreases epithelial differentiation and absorptive function. The close association of several IHC parameters with manual histologic scoring suggests that automated digital quantification of IHC panels complements traditional histomorphologic assessment in EED.
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