Department of Pediatrics, Division of Gastroenterology and Nutrition
Bacterial Infections and Mycoses | Digestive System Diseases | Gastroenterology | Pediatrics | Public Health
BACKGROUND: Environmental Enteric Dysfunction (EED) in children from low-income countries has been linked to linear growth declines. There is a critical need to identify sensitive and early EED biomarkers.
OBJECTIVE: Determine whether levels of antibodies against bacterial components flagellin (flic) and lipopolysaccharide (LPS) predict poor growth.
DESIGN/METHODS: In a prospective birth cohort of 380 children in rural Pakistan blood and stool samples were obtained at ages 6 and 9 months. Linear mixed effects models were used to examine longitudinal associations between quartiles of anti-flic and anti-LPS antibodies and changes in LAZ, WAZ and WLZ scores. Spearman's correlations were measured between anti-flic and anti-LPS immunoglobulins with measures of systemic/enteric inflammation and intestinal regeneration.
RESULTS: Anti-LPS IgA correlated significantly with CRP, AGP and Reg1 serum at 6mo and with MPO at 9mo. In multivariate analysis at 6mo of age, higher anti-LPS IgA levels predicted greater declines in LAZ scores over subsequent 18mo (comparing highest to lowest quartile, beta (SE) change in LAZ score/year = -0.313 (0.125), p-value = 0.013). Anti-flic Ig A in the two highest quartiles measured at 9mo of age had declines in LAZ of -0.269 (0.126), p = 0.033; and -0.306 (0.129), p = 0.018 respectively, during the subsequent 18mo of life, compared to those in the lowest quartile of anti-flic IgA.
CONCLUSIONS AND RELEVANCE: Elevated anti-flic IgA and anti-LPS IgA antibodies at 6 and 9mo, predict declines in linear growth. Systemic and enteric inflammation correlated with anti-LPS IgA provides mechanistic considerations for potential future interventions.
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Copyright: © 2018 Syed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2018 Mar 6;13(3):e0193768. doi: 10.1371/journal.pone.0193768.. Link to article on publisher's site
Syed S, Iqbal NT, Sadiq K, Ma JZ, Akhund T, Xin W, Moore SR, Liu E, Qureshi S, Gosselin KB, Gewirtz A, Duggan CP, Ali SA. (2018). Serum anti-flagellin and anti-lipopolysaccharide immunoglobulins as predictors of linear growth faltering in Pakistani infants at risk for environmental enteric dysfunction. Pediatric Publications and Presentations. https://doi.org/10.1371/journal.pone.0193768. Retrieved from https://escholarship.umassmed.edu/peds_pp/211
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