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\begin{document}

\title{Noninvasive Biomarkers Identify Eosinophilic Esophagitis: A Prospective
Longitudinal Study in Children}



\author[1]{Joshua Wechsler}%
\author[2]{Steven Ackerman}%
\author[3]{Mirna Chehade}%
\author[1]{Katie Amsden}%
\author[3]{Mary Ellen Riffle}%
\author[1]{Ming-Yu Wang}%
\author[2]{Jian Du}%
\author[2]{Matthew Kleinjan}%
\author[2]{Preeth Alumkal}%
\author[4]{Elizabeth Gray}%
\author[4]{Kwang-Youn Kim}%
\author[1]{Barry Wershil}%
\author[1]{Amir Kagalwalla}%
\affil[1]{Ann \& Robert H. Lurie Children’s Hospital}%
\affil[2]{University of Illinois at Chicago}%
\affil[3]{Mount Sinai School of Medicine}%
\affil[4]{Northwestern University Feinberg School of Medicine}%


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  \date{May 24, 2024}


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\begin{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.%
\end{abstract}%



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