Multiplexed immunohistochemical evaluation of small bowel inflammatory and epithelial parameters in environmental enteric dysfunction.

Autor:	VanBuskirk K; Department of Global Health, University of Washington School of Public Health, Seattle, WA, United States., Mweetwa M; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia., Kolterman T; Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, United States., Raghavan S; Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, United States., Ahmed T; Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh., Ali SA; Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan., Begum SKN; Department of Pathology, Bangladesh Specialized Hospital, Dhaka, Bangladesh., Besa E; Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Lusaka, Zambia., Denno DM; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, United States., Jamil Z; Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan., Kelly P; Blizard Institute, Barts & the London School of Medicine, Queen Mary University of London, London, United Kingdom., Mahfuz M; Nutrition Research Division, International Centre for Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh., Moore SR; Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA, United States., Mouksassi S; Certara, Princeton, NJ, United States., Petri WA Jr; Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA, United States., Tarr PI; Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, United States., Sullivan PB; Department of Paediatrics, Children's Hospital, University of Oxford, Oxford, United Kingdom., Moskaluk CA; Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, United States. Electronic address: cam5p@virginia.edu.
Jazyk:	angličtina
Zdroj:	The American journal of clinical nutrition [Am J Clin Nutr] 2024 Sep; Vol. 120 Suppl 1, pp. S31-S40.
DOI:	10.1016/j.ajcnut.2024.02.033
Abstrakt:	Background: Environmental enteric dysfunction (EED) is characterized by reduced absorptive capacity and barrier function of the small intestine, leading to poor ponderal and linear childhood growth. Objectives: To further define gene expression patterns that are associated with EED to uncover new pathophysiology of this disorder. Methods: Duodenal 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. Results: After 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. Conclusions: Our 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. (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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