Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis.
OBJECTIVE
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/muL, 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.
Konikoff
Michael R
MR
Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039, USA.
Blanchard
Carine
C
Kirby
Cassie
C
Buckmeier
Bridget K
BK
Cohen
Mitchell B
MB
Heubi
James E
JE
Putnam
Philip E
PE
Rothenberg
Marc E
ME
D000293:Adolescent; D015415:Biomarkers / Q000097:blood*; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D047208:Eosinophil-Derived Neurotoxin / Q000097:blood*; D004802:Eosinophilia / Q000097:blood / Q000175:diagnosis*; D004804:Eosinophils; D004941:Esophagitis / Q000097:blood / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000097:blood*; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity
D015415:Biomarkers; C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D007155:Immunologic Factors; D047208:Eosinophil-Derived Neurotoxin