Syed, SanaIqbal, Najeeha T.Sadiq, KamranMa, Jennie Z.Akhund, TauseefXin, WenjunMoore, Sean R.Liu, EnjuQureshi, ShahidaGosselin, KerriGewirtz, AndrewDuggan, ChristopherAli, S. Asad2018-04-192018Syed, S., N. T. Iqbal, K. Sadiq, J. Z. Ma, T. Akhund, W. Xin, S. R. Moore, et al. 2018. “Serum anti-flagellin and anti-lipopolysaccharide immunoglobulins as predictors of linear growth faltering in Pakistani infants at risk for environmental enteric dysfunction.” PLoS ONE 13 (3): e0193768. doi:10.1371/journal.pone.0193768. http://dx.doi.org/10.1371/journal.pone.0193768.http://nrs.harvard.edu/urn-3:HUL.InstRepos:35982234Background: 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, 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. 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.en-USPeople and PlacesPopulation GroupingsAge GroupsChildrenInfantsFamiliesBiology and Life SciencesPhysiologyImmune PhysiologyAntibodiesMedicine and Health SciencesImmunologyImmune System ProteinsBiochemistryProteinsBiomarkersImmune ResponseInflammationDiagnostic MedicineSigns and SymptomsPathology and Laboratory MedicineMicrobiologyBacteriologyBacterial PhysiologyFlagellinMicrobial PhysiologyAnatomyDigestive SystemGastrointestinal TractProtein ComplexesFerritinJournal Article2018-04-1910.1371/journal.pone.0193768