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Noninvasive Biomarkers Identify Eosinophilic Esophagitis: A Prospective Longitudinal Study in Children
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  • Joshua Wechsler,
  • Steven Ackerman,
  • Mirna Chehade,
  • Katie Amsden,
  • Mary Ellen Riffle,
  • Ming-Yu Wang,
  • Jian Du,
  • Matthew Kleinjan,
  • Preeth Alumkal,
  • Elizabeth Gray,
  • Kwang-Youn Kim,
  • Barry Wershil,
  • Amir Kagalwalla
Joshua Wechsler
Ann & Robert H. Lurie Children’s Hospital
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Steven Ackerman
University of Illinois at Chicago
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Mirna Chehade
Mount Sinai School of Medicine
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Katie Amsden
Ann & Robert H. Lurie Children’s Hospital
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Mary Ellen Riffle
Mount Sinai School of Medicine
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Ming-Yu Wang
Ann & Robert H. Lurie Children’s Hospital
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Jian Du
University of Illinois at Chicago
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Matthew Kleinjan
University of Illinois at Chicago
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Preeth Alumkal
University of Illinois at Chicago
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Elizabeth Gray
Northwestern University Feinberg School of Medicine
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Kwang-Youn Kim
Northwestern University Feinberg School of Medicine
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Barry Wershil
Ann & Robert H. Lurie Children’s Hospital
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Amir Kagalwalla
Ann & Robert H. Lurie Children’s Hospital
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Abstract

Background: Esophageal histology is critical for diagnosis and surveillance of disease activity in eosinophilic esophagitis (EoE). A validated noninvasive biomarker has not been identified. We aimed to determine the utility of blood and urine eosinophil-associated proteins to identify EoE diagnosis and predict esophageal eosinophilia. Methods: Blood and urine were collected from children undergoing endoscopy with biopsy. Absolute eosinophil count (AEC), plasma eosinophil-derived neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein-1 (MBP-1), galectin-10 (CLC/GAL-10), Eotaxin-2 and Eotaxin-3, and urine osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9) were determined. Differences were assessed between EoE and control, and with treatment response. The capacity to predict EoE diagnosis and esophageal eosinophil counts was assessed. Results: 183 specimens were collected from 56 EoE patients and 15 non-EoE patient controls; 33 EoE patients had paired pre- and post-treatment specimens. Plasma (CLC/GAL-10, ECP, EDN, Eotaxin-3, MBP-1) and urine (OPN) biomarkers were increased in EoE compared to control. A panel comprising CLC/GAL-10, Eotaxin-3, ECP, EDN, MBP-1, and AEC was superior to AEC alone in distinguishing EoE from control. AEC, CLC/GAL-10, ECP, and MBP-1 were significantly decreased in patients with a good response to treatment compared to patients with a poor response. AEC, CLC/GAL-10, ECP, EDN, OPN, and MBP-1 each predicted esophageal eosinophil counts utilizing mixed models controlled for age, gender, treatment and atopy; AEC combined with MBP-1 best predicted the counts. Conclusions: We identified novel panels of eosinophil-associated proteins that along with AEC are superior to AEC alone in distinguishing EoE from control and predicting esophageal eosinophil counts.

Peer review status:Published

23 Oct 2020Submitted to Allergy
26 Oct 2020Submission Checks Completed
26 Oct 2020Assigned to Editor
28 Oct 2020Reviewer(s) Assigned
16 Nov 2020Review(s) Completed, Editorial Evaluation Pending
17 Nov 2020Editorial Decision: Revise Minor
11 Mar 20211st Revision Received
15 Mar 2021Submission Checks Completed
15 Mar 2021Assigned to Editor
16 Mar 2021Reviewer(s) Assigned
30 Mar 2021Review(s) Completed, Editorial Evaluation Pending
31 Mar 2021Editorial Decision: Accept
27 Apr 2021Published in Allergy. 10.1111/all.14874