Elevations in serum anti-flagellin and anti-LPS Igs are related to growth faltering in young Tanzanian children

Christine M. McDonald, Boston Children’s Hospital
Karim P. Manji, Muhimbili University of Health and Allied Sciences
Kerri B. Gosselin, University of Massachusetts Medical School
Hao Q. Tran, Georgia State University
Enju Liu, Harvard T.H. Chan School of Public Health
Rodrick Kisenge, Muhimbili University of Health and Allied Sciences
Said Aboud, Muhimbili University of Health and Allied Sciences
Wafaie W. Fawzi, Harvard T.H. Chan School of Public Health
Andrew T. Gewirtz, Georgia State University
Christopher P. Duggan, Boston Children’s Hospital

At the time of publication, Kerri B. Gosselin was not yet affiliated with the University of Massachusetts Medical School.

Abstract

BACKGROUND: Antibodies to LPS and flagellin have been described as indirect measures of increased gastrointestinal permeability and may be markers of environmental enteric dysfunction (EED), which is a condition associated with poor child growth.

OBJECTIVE: We assessed whether LPS- and flagellin-specific immunoglobulin (Ig) concentrations were associated with poor growth in young Tanzanian children at risk of EED. DESIGN: Blood samples were obtained from 590 childre

RESULTS: Anti-LPS and anti-flagellin IgA and IgG concentrations increased over the first year of life and were higher than concentrations (measured at 9 mo of age) in healthy controls. Children with anti-flagellin IgA, anti-LPS IgA, anti-flagellin IgG, and anti-LPS IgG concentrations in the highest quartile at 6 wk of age were 2.02 (95% CI: 1.11, 3.67), 1.84 (95% CI: 1.03, 3.27), 1.94 (95% CI: 1.04, 3.62), and 2.31 (95% CI: 1.25, 4.27) times, respectively, more likely to become underweight (weight-for-age z score < -2) after adjustment for covariates (P-trend < 0.05) than were children with Ig concentrations in the lowest quartile. Children with increased concentrations of anti-flagellin IgA were also more likely to become wasted; however, there was no association between any of the markers and subsequent stunting.

CONCLUSION: Serologic measures of increased intestinal permeability to bacterial components are associated with subsequent poor growth and could help identify children who may benefit most from preventive interventions. This trial was registered at clinicaltrials.gov as NCT00421668.