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Exploring Potential Noninvasive Biomarkers in Eosinophilic Esophagitis in Children

Subbarao, Girish*; Rosenman, Marc B.; Ohnuki, Lyo; Georgelas, Ann; Davis, Miriam*; Fitzgerald, Joseph F.*; Molleston, Jean P.*; Croffie, Joseph M.*; Pfefferkorn, Marian D.*; Corkins, Mark R.*; Lim, Joel R.*; Steiner, Steven J.*; Schaefer, Elizabeth§; Gleich, Gerald J.; Gupta, Sandeep K.*

Journal of Pediatric Gastroenterology & Nutrition: December 2011 - Volume 53 - Issue 6 - p 651–658
doi: 10.1097/MPG.0b013e318228cee6
Original Articles: Gastroenterology

Background and Aims: Eosinophilic esophagitis (EE) continues to present clinical challenges, including a need for noninvasive tools to manage the disease. To identify a marker able to assess disease status in lieu of repeated endoscopies, we examined 3 noninvasive biomarkers, serum interleukin (IL)-5, serum eosinophil-derived neurotoxin (EDN), and stool EDN, and examined possible correlations of these with disease phenotype and activity (symptoms and histology) in a longitudinal study of children with EE.

Subjects and Methods: Children with EE were studied for up to 24 weeks (12 weeks on 1 of 2 corticosteroid therapies and 12 weeks off therapy). Twenty children with normal esophagogastroduodenoscopies with biopsies were enrolled as controls. Serum IL-5, serum EDN, and stool EDN were measured at weeks 0, 4, 12, 18, and 24 in children with EE, and at baseline alone for controls. Primary and secondary statistical analyses (excluding and including outlier values of the biomarkers, respectively) were performed.

Results: Sixty subjects with EE (46 [75%] boys, mean age 7.5 ± 4.4 years) and 20 normal controls (10 [50%] boys, mean age 6.7 ± 4.1 years) were included. Significant changes in serum EDN (significant decrease from baseline to week 4, and then rebound from week 4 to week 12) occurred. Serum EDN levels were stable after week 12. Serum IL-5 and stool EDN levels in subjects with EE were not statistically different from those of the control subjects when each time point for the cases was compared with the controls’ 1-time measurement.

Conclusions: Serum EDN levels were significantly higher in subjects with EE than in controls, and the results suggest a possible role, after additional future studies, for serum EDN in establishing EE diagnosis, assessing response to therapy, and/or monitoring for relapse or quiescence.

*Division of Pediatric Gastroenterology/Hepatology/Nutrition, Indiana University School of Medicine, Indianapolis

Children's Health Services Research and Regenstrief Institute, Indiana University School of Medicine, Indianapolis

Department of Dermatology, University of Utah, Salt Lake City

§St Vincent Hospital, Indianapolis, IN.

Address correspondence and reprint requests to Sandeep Gupta, MD, Division of Pediatric Gastroenterology/Hepatology/Nutrition, Indiana University School of Medicine/Riley Hospital for Children, 702 Barnhill Dr, ROC 4210, Indianapolis, IN 46202 (e-mail:

Received 18 August, 2010

Accepted 3 June, 2011

This study was supported by a Clarian Values grant, Clarian Health Partners, Inc, Indianapolis, IN.

Sandeep K. Gupta, MD, is a consultant for Abbott Nutrition. The other authors report no conflicts of interest.

Copyright 2011 by ESPGHAN and NASPGHAN