Article Text

Download PDFPDF

Original article
The oesophageal string test: a novel, minimally invasive method measures mucosal inflammation in eosinophilic oesophagitis
  1. Glenn T Furuta1,2,3,4,
  2. Amir F Kagalwalla5,6,
  3. James J Lee7,
  4. Preeth Alumkal8,
  5. Brian T Maybruck8,
  6. Sophie Fillon1,2,3,
  7. Joanne C Masterson1,2,3,
  8. Sergei Ochkur7,
  9. Cheryl Protheroe7,
  10. Wendy Moore1,2,3,4,
  11. Zhaoxing Pan1,3,
  12. Katie Amsden5,
  13. Zachary Robinson1,2,
  14. Kelley Capocelli1,9,
  15. Vince Mukkada1,2,3,
  16. Dan Atkins1,4,
  17. David Fleischer1,4,
  18. Lindsay Hosford1,2,3,
  19. Mark A Kwatia8,
  20. Shauna Schroeder1,2,3,
  21. Caleb Kelly1,2,
  22. Mark Lovell1,9,
  23. Hector Melin-Aldana5,10,
  24. Steven J Ackerman8
  1. 1Department of Pediatrics, Gastrointestinal Eosinophilic Diseases Program, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
  2. 2Mucosal Inflammation Program, University of Colorado Denver School of Medicine, Aurora, Colorado, USA
  3. 3Digestive Health Institute, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Children's Hospital Colorado, Aurora, Colorado, USA
  4. 4Department of Pediatrics, National Jewish Health, Denver, Colorado, USA
  5. 5Department of Pediatrics, Ann and Robert H Lurie Children's Hospital of Chicago and Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA
  6. 6Department of Pediatrics, John H. Stroger Hospital of Cook County, Chicago, Illinois, USA
  7. 7Department of Biochemistry and Molecular Biology, Mayo Clinic, Scottsdale, Arizona, USA
  8. 8Departments of Biochemistry and Molecular Genetics, and Medicine, College of Medicine, University of Illinois at Chicago, Illinois, USA
  9. 9Department of Pathology, University of Colorado Denver School of Medicine, Colorado, USA
  10. 10Department of Pathology, Ann and Robert H Lurie Children's Hospital of Chicago and Northwestern University, Chicago, Illinois, USA
  1. Correspondence to Dr Glenn T Furuta, 13123 East 16th Ave, B290, Aurora, CO 80045, USA; glenn.furuta{at}childrenscolorado.org and Dr Steven J Ackerman, MBRB Rm. 2074, MC669 UIC, 900 South Ashland Ave, Chicago, IL 60007, USA; sackerma{at}uic.edu

Abstract

Objective Eosinophil predominant inflammation characterises histological features of eosinophilic oesophagitis (EoE). Endoscopy with biopsy is currently the only method to assess oesophageal mucosal inflammation in EoE. We hypothesised that measurements of luminal eosinophil-derived proteins would correlate with oesophageal mucosal inflammation in children with EoE.

Design The Enterotest diagnostic device was used to develop an oesophageal string test (EST) as a minimally invasive clinical device. EST samples and oesophageal mucosal biopsies were obtained from children undergoing upper endoscopy for clinically defined indications. Eosinophil-derived proteins including eosinophil secondary granule proteins (major basic protein-1, eosinophil-derived neurotoxin, eosinophil cationic protein, eosinophil peroxidase) and Charcot–Leyden crystal protein/galectin-10 were measured by ELISA in luminal effluents eluted from ESTs and extracts of mucosal biopsies.

Results ESTs were performed in 41 children with active EoE (n=14), EoE in remission (n=8), gastro-oesophageal reflux disease (n=4) and controls with normal oesophagus (n=15). EST measurement of eosinophil-derived protein biomarkers significantly distinguished between children with active EoE, treated EoE in remission, gastro-oesophageal reflux disease and normal oesophagus. Levels of luminal eosinophil-derived proteins in EST samples significantly correlated with peak and mean oesophageal eosinophils/high power field (HPF), eosinophil peroxidase indices and levels of the same eosinophil-derived proteins in extracts of oesophageal biopsies.

Conclusions The presence of eosinophil-derived proteins in luminal secretions is reflective of mucosal inflammation in children with EoE. The EST is a novel, minimally invasive device for measuring oesophageal eosinophilic inflammation in children with EoE.

  • Eosinophil
  • pediatric
  • enterotest string test
  • oesophagitis
  • inflammation
  • epithelial barrier
  • gastrointestinal tract
  • oesophageal disease
  • oesophageal disorders
  • oesophageal lesions
  • oesophageal reflux
  • oesophageal strictures
  • allergy
  • breast milk
  • childhood nutrition

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/

View Full Text

Statistics from Altmetric.com

Supplementary materials

Footnotes

  • Disclosure The contents are the authors' sole responsibility and do not represent official NIH views.

  • Funding This work supported in part by grants or gifts from NIH–R21AI079925 (GTF/SJA), Thrasher Research Fund (GTF/SJA), supported by NIH/NCATS Colorado CCTSI grant number UL1 TR000154 (GTF). Shell, Mandell, Boyd and Savoie Families (GTF), American Gastroenterological Association (GTF/SJA), Campaign Urging Research for Eosinophilic Diseases (SJA/GTF), Buckeye Foundation (AFK), Pappas Foundation (GTF), American Partnership for Eosinophilic Disorders (SJA/AFK/GTF), Sandhill Scientific (GTF/SJA), Mayo Foundation and NIH HL058732 (PI: Nancy A. Lee, JJL), and the NCRR K26 RR0109709 (JJL), NIH- 1UL1RR025741 (AFK).

  • Competing interests None.

  • Ethics approval Ethics approval was provided by the Colorado Multi-Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data measuring gastric protein levels are available for public review.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.