Clinical Gastroenterology and Hepatology
Volume 4, Issue 11 , Pages 1328-1336, November 2006

Potential of Blood Eosinophils, Eosinophil-Derived Neurotoxin, and Eotaxin-3 as Biomarkers of Eosinophilic Esophagitis

  • Michael R. Konikoff

      Affiliations

    • Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    • ,
  • Carine Blanchard

      Affiliations

    • Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
    • ,
  • Cassie Kirby

      Affiliations

    • Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
    • ,
  • Bridget K. Buckmeier

      Affiliations

    • Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
    • ,
  • Mitchell B. Cohen

      Affiliations

    • Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    • ,
  • James E. Heubi

      Affiliations

    • Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    • ,
  • Philip E. Putnam

      Affiliations

    • Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
    • ,
  • Marc E. Rothenberg

      Affiliations

    • Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio
    • Corresponding Author InformationAddress requests for reprints to: Marc E. Rothenberg, MD, PhD, Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, MLC 7028, Cincinnati, Ohio 45229-3039; fax: (513) 636-3310.

published online 27 October 2006.

Background & Aims: Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. Methods: A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. Results: AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/μL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. Conclusions: These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.

Abbreviations used in this paper: AEC, absolute eosinophil count, EDN, eosinophil-derived neurotoxin, EE, eosinophilic esophagitis, ELISA, enzyme-linked immunosorbent assay, HPF, high-power field, IL, interleukin

 

 Supported by the Burroughs Wellcome Fund, the CURED Foundation, the Buckeye Foundation, and a grant from the National Institutes of Health (T32 DK007727).

PII: S1542-3565(06)00805-6

doi:10.1016/j.cgh.2006.08.013

Clinical Gastroenterology and Hepatology
Volume 4, Issue 11 , Pages 1328-1336, November 2006