TY - JOUR
T1 - Noninvasive biomarkers identify eosinophilic esophagitis
T2 - A prospective longitudinal study in children
AU - Wechsler, Joshua B.
AU - Ackerman, Steven J.
AU - Chehade, Mirna
AU - Amsden, Katie
AU - Riffle, Mary E.
AU - Wang, Ming Yu
AU - Du, Jian
AU - Kleinjan, Matt L.
AU - Alumkal, Preeth
AU - Gray, Elizabeth
AU - Kim, Kwang Youn A.
AU - Wershil, Barry K.
AU - Kagalwalla, Amir F.
N1 - Funding Information:
The authors thank the American Partnership for Eosinophilic Disorders (APFED), Buckeye Foundation, Ann & Robert H. Lurie Children’s Hospital of Chicago, and Consortium of Eosinophilic Gastrointestinal Researchers (CEGIR) for their financial support of the study. Dr. Wechsler was a scholar trainee in CEGIR, part of the Rare Disease Clinical Research Network, an initiative of the National Institutes of Health Office of Rare Diseases Research, National Center for Advancing Translational Sciences, funded through collaboration between the National Institute of Allergy and Infectious Disease, National Institute of Diabetes, Digestive, and Kidney Diseases, and Nation Center for Advancing Translational Sciences. The authors also thank the pediatric patients and their parents for participating in the study, and the patient advocacy groups American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Diseases (CURED) and Eosinophil Family Coalition for their support of CEGIR.
Funding Information:
This work was supported in part by a HOPE pilot grant from the American Partnership for Eosinophilic Disorders (APFED) (to AFK, BKW, SJA), Buckeye Foundation (to AFK and MC), K08DK097721 (to JBW), internal funding from Ann & Robert H. Lurie Children's Hospital of Chicago, and Consortium of Eosinophilic Gastrointestinal Researchers (CEGIR) [to JBW]. Dr. Wechsler was a trainee scholar in CEGIR (U54 AI117804) part of the Rare Disease Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, and is funded through collaboration between National Institute of Allergy and Infectious Disease, National Institute of Diabetes, Digestive, and Kidney Diseases, and Nation Center for Advancing Translational Sciences. CEGIR is also supported by patient advocacy groups including American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Diseases and Eosinophil Family Coalition
Funding Information:
This work was supported in part by a HOPE pilot grant from the American Partnership for Eosinophilic Disorders (APFED) (to AFK, BKW, SJA), Buckeye Foundation (to AFK and MC), K08DK097721 (to JBW), internal funding from Ann & Robert H. Lurie Children's Hospital of Chicago, and Consortium of Eosinophilic Gastrointestinal Researchers (CEGIR) [to JBW]. Dr. Wechsler was a trainee scholar in CEGIR (U54 AI117804) part of the Rare Disease Clinical Research Network, an initiative of the Office of Rare Diseases Research, National Center for Advancing Translational Sciences, and is funded through collaboration between National Institute of Allergy and Infectious Disease, National Institute of Diabetes, Digestive, and Kidney Diseases, and Nation Center for Advancing Translational Sciences. CEGIR is also supported by patient advocacy groups including American Partnership for Eosinophilic Disorders, Campaign Urging Research for Eosinophilic Diseases and Eosinophil Family Coalition The authors thank the American Partnership for Eosinophilic Disorders (APFED), Buckeye Foundation, Ann & Robert H. Lurie Children?s Hospital of Chicago, and Consortium of Eosinophilic Gastrointestinal Researchers (CEGIR) for their financial support of the study. Dr. Wechsler was a scholar trainee in CEGIR, part of the Rare Disease Clinical Research Network, an initiative of the National Institutes of Health Office of Rare Diseases Research, National Center for Advancing Translational Sciences, funded through collaboration between the National Institute of Allergy and Infectious Disease, National Institute of Diabetes, Digestive, and Kidney Diseases, and Nation Center for Advancing Translational Sciences. The authors also thank the pediatric patients and their parents for participating in the study, and the patient advocacy groups American Partnership for Eosinophilic Disorders (APFED), Campaign Urging Research for Eosinophilic Diseases (CURED) and Eosinophil Family Coalition for their support of CEGIR.
Publisher Copyright:
© 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd
PY - 2021/12
Y1 - 2021/12
N2 - 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 diagnose EoE 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: Of 183 specimens were collected from 56 EoE patients and 15 non-EoE controls with symptoms of esophageal dysfunction; 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 esophageal eosinophil counts <15/hpf in response to treatment. 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 controls and predicting esophageal eosinophil counts.
AB - 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 diagnose EoE 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: Of 183 specimens were collected from 56 EoE patients and 15 non-EoE controls with symptoms of esophageal dysfunction; 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 esophageal eosinophil counts <15/hpf in response to treatment. 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 controls and predicting esophageal eosinophil counts.
KW - biomarker
KW - blood
KW - eosinophil
KW - eosinophilic esophagitis
KW - noninvasive
UR - http://www.scopus.com/inward/record.url?scp=85105496428&partnerID=8YFLogxK
U2 - 10.1111/all.14874
DO - 10.1111/all.14874
M3 - Article
C2 - 33905577
AN - SCOPUS:85105496428
SN - 0105-4538
VL - 76
SP - 3755
EP - 3765
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 12
ER -