Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia.

Abstract

Intestinal damage in malnutrition constitutes a threat to the survival of many thousands of children globally. We studied children in Lusaka, Zambia, with severe acute malnutrition (SAM) and persistent diarrhea using endoscopy, biopsy and analysis of markers and protective proteins in blood and intestinal secretions. We carried out parallel investigations in apparently healthy adults, and analyzed biomarkers only in apparently healthy children. Villus height and crypt depth did not differ in children with SAM and adult controls, but epithelial surface was reduced in children with SAM (median 445, interquartile range (IQR) 388, 562μm per 100μm muscularis mucosae) compared to adults (578, IQR 465,709; P=0.004). Histological lesions and disruptions of claudin-4 and E-cadherin were most pronounced in children with SAM. Circulating lipopolysaccharide, a marker of bacterial translocation, was higher in malnourished children (251, IQR 110,460EU/ml) than in healthy children (51, IQR 0,111; P=0.0001). Other translocation markers showed similar patterns. Anti-Deamidated Gliadin Peptide IgG concentrations, although within the normal range, were higher in children with SAM (median 2.7U/ml, IQR 1.5-8.6) than in adults (1.6, 1.4-2.1; P=0.005), and were inversely correlated with villus height (ρ=-0.79, n=13, P=0.001). Malnutrition enteropathy is associated with intestinal barrier failure and immune dysregulation.

• Authors: Beatrice Amadi, Ellen Besa, Kanekwa Zyambo, Patrick Kaonga, John Louis-Auguste, Kanta Chandwe, Phillip I Tarr, Donna M Denno, James P Nataro, William Faubion, Anne Sailer, Sunil Yeruva, Tricia Brantner, Joseph Murray, Andrew J Prendergast, Jerrold R Turner, Paul Kelly
• Journal: EBioMedicine (EBioMedicine) Vol. 22 Pg. 191-199 (Aug 2017) ISSN: 2352-3964 [Electronic] Netherlands
• PMID: 28750860 (Publication Type: Journal Article)
• Copyright: Copyright © 2017. Published by Elsevier B.V.

Chemical References

• Antigens, CD
• Autoantibodies
• Biomarkers
• CDH1 protein, human
• CLDN4 protein, human
• Cadherins
• Claudin-4
• Lipopolysaccharides

Topics

• Antigens, CD
• Autoantibodies (metabolism)
• Biomarkers (blood, metabolism)
• Biopsy
• Cadherins (metabolism)
• Child
• Child, Preschool
• Claudin-4 (metabolism)
• Cross-Sectional Studies
• Diarrhea (diagnosis, immunology)
• Endoscopy, Gastrointestinal
• Female
• Humans
• Lipopolysaccharides (blood)
• Male
• Severe Acute Malnutrition (diagnosis, immunology)