Serum anti-flagellin and anti-lipopolysaccharide immunoglobulins as predictors of linear growth faltering in Pakistani infants at risk for environmental enteric dysfunction

• Published in: PloS one Vol. 13; no. 3; p. e0193768
• Main Authors: Syed, Sana, Iqbal, Najeeha T, Sadiq, Kamran, Ma, Jennie Z, Akhund, Tauseef, Xin, Wenjun, Moore, Sean R, Liu, Enju, Qureshi, Shahida, Gosselin, Kerri, Gewirtz, Andrew, Duggan, Christopher P, Ali, S Asad
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.03.2018; Public Library of Science (PLoS)
• Subjects: Antibodies; Asymptomatic Infections; Bacterial infections; Biology and Life Sciences; Biomarkers; Biomarkers - blood; Child Development; Children; Correlation analysis; E coli; Escherichia coli; Feces - microbiology; Female; Flagellin; Flagellin - immunology; Follow-Up Studies; Gastroenterology; Gene expression; Health sciences; Hepatology; Hospitals; Humans; Immune system; Immunoglobulin A; Immunoglobulin A - blood; Immunoglobulins; Infant; Infants; Infections; Infections - complications; Inflammation; Inflammatory bowel disease; Intestinal Diseases - epidemiology; Intestinal Diseases - immunology; Intestinal Diseases - microbiology; Intestine; Linear Models; Lipopolysaccharides; Lipopolysaccharides - immunology; Longitudinal Studies; Male; Malnutrition; Malnutrition - complications; Medicine and Health Sciences; Multivariate Analysis; Nutrition; Pakistan; Pediatrics; People and Places; Permeability; Physiology; Prospective Studies; Public health; Quartiles; Regeneration; Risk; Rural Population; Salmonella; Salmonella Typhimurium; Small intestine; Pakistan; United States > US; Karachi Pakistan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0193768

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. Determine whether levels of antibodies against bacterial components flagellin (flic) and lipopolysaccharide (LPS) predict poor growth. 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. 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, β (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. 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.