Impaired Barrier Function and Autoantibody Generation in Malnutrition Enteropathy in Zambia

EBioMedicine

Andrew J. Prendergast¹  Beatrice Amadi²  Kanta Chandwe²  James P. Nataro³  Donna M. Denno⁴  Phillip I. Tarr⁵  Sunil Yeruva⁶  Anne Sailer⁶  Jerrold R. Turner⁶  William Faubion⁷  Joseph Murray⁷  Tricia Brantner⁷  Patrick Kaonga⁸  John Louis-Auguste⁸  Paul Kelly⁸  Ellen Besa⁸  Kanekwa Zyambo⁸ 

[1] Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK;Department of Paediatrics, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia;Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, USA;Department of Pediatrics, University of Washington, Seattle, USA;Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA;Departments of Pathology and Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA;Mayo Clinic, Rochester, MN, USA;Tropical Gastroenterology and Nutrition Group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia;

关键词: Enteropathy;    Environmental enteric dysfunction;    HIV;    Malnutrition;    Glucagon-like peptide 2;    Microbial translocation;    Autoantibodies;    Tissue transglutaminase serology, deamidated gliadin peptide serology;   

DOI  :  10.1016/j.ebiom.2017.07.017

来源: DOAJ

【 摘 要 】

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, 562 μm per 100 μm 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 110,460 EU/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 2.7 U/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.

【 授权许可】

Unknown