title: Eosinophil Quantitated Urine Kinetic: A novel assay for assessment of eosinophilic esophagitis.
abstract: Eosinophilic esophagitis (EoE) is a chronic disease that requires long-term medical management and monitoring. The eosinophil count determined during esophageal biopsy remains the gold standard for diagnosis and monitoring of EoE. Although markers of eosinophil degranulation correlate with symptoms, eosinophil counts do not correlate. Development of a noninvasive, cost-effective biomarker of eosinophil activation for the evaluation of EoE is an unmet medical need.
  
  
  
  To conduct a proof-of-concept study to evaluate the potential for measuring urinary 3-bromotyrosine (3-BT) levels in creatinine normalized urine for quantifying eosinophil degranulation in EoE disease.
  
  
  
  A mass spectrometry-based method of measuring normalized 3-BT levels, the Eosinophil Quantitated Urine Kinetic (EoQUIK), was developed, and proof-of-concept evaluation was performed for patients with EoE (n = 27), atopic controls (n = 24), and nonatopic controls (n = 24).
  
  
  
  EoQUIK revealed that median normalized 3-BT levels were increased 93-fold in patients with EoE compared with nonatopic controls (P = .01) and increased 13-fold in patients with EoE compared with atopic controls (P = .01). Cutoff thresholds were selected for EoQUIK that yielded a specificity of 100% and a negative predictive value of 100% for nonatopic controls and a specificity of 79% and a negative predictive value of 90% for atopic controls. In a logistic regression model, a urine 3-BT level greater than 20 pg per 400 mg of creatinine increased the odds of a patient having EoE by 4.8 (95% confidence interval, 1.14-20.5; P = .03) when compared with atopic controls after controlling for race and sex.
  
  
  
  These data provide proof of concept that EoQUIK can potentially be a useful noninvasive clinical tool in the evaluation of possible EoE.
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia; Children's Specialty Group, Norfolk, Virginia; Children's Hospital of The King's Daughters, Norfolk, Virginia; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia. Electronic address: cunniokm@evms.edu.
authors.forename: Kenji M
authors.initials: KM
authors.lastname: Cunnion
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia; Children's Specialty Group, Norfolk, Virginia; Children's Hospital of The King's Daughters, Norfolk, Virginia.
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Willis
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Minto
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia; The Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Tanya C
authors.initials: TC
authors.lastname: Burch
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia; Children's Specialty Group, Norfolk, Virginia; Children's Hospital of The King's Daughters, Norfolk, Virginia.
authors.forename: Alice L
authors.initials: AL
authors.lastname: Werner
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia; Children's Specialty Group, Norfolk, Virginia; Children's Hospital of The King's Daughters, Norfolk, Virginia; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Tushar A
authors.initials: TA
authors.lastname: Shah
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia; Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Neel K
authors.initials: NK
authors.lastname: Krishna
authors.affiliation: Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, Virginia; The Leroy T. Canoles Jr. Cancer Research Center, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Julius O
authors.initials: JO
authors.lastname: Nyalwidhe
authors.affiliation: Department of Pediatrics, Eastern Virginia Medical School, Norfolk, Virginia; Children's Specialty Group, Norfolk, Virginia; Children's Hospital of The King's Daughters, Norfolk, Virginia.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Maples
mesh_terms: D000293:Adolescent; D000328:Adult; D001681:Biological Assay; D002648:Child; D002675:Child, Preschool; D057765:Eosinophilic Esophagitis / Q000175:diagnosis / Q000276:immunology / Q000652:urine*; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000652:urine; D055815:Young Adult
chemical_list: D014443:Tyrosine; C118327:3-bromotyrosine