{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T23:08:16Z","timestamp":1779059296259,"version":"3.51.4"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T00:00:00Z","timestamp":1725580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Proton pump inhibitors (PPIs) are one of the standards of care of eosinophilic esophagitis (EoE) treatment, though PPI response rates are variable ranging from 23 to 63% in pediatric studies. We sought to determine if expression of select genes in esophageal mucosa can predict PPI responsiveness in EoE. Children with a new diagnosis of EoE (15 or more eosinophils\/hpf on esophageal biopsy) were prospectively treated with 8\u00a0weeks of PPI therapy before follow-up esophagogastroduodenoscopy (EGD). Children with &amp;lt;15 eosinophils\/hpf on follow-up were classified as having PPI-Responsive EoE (PPI-R) and\u2009\u2265\u200915 eosinophils\/hpf as PPI-Nonresponsive EoE (PPI-NR). Using the Nanostring nCounter Analysis System, mRNA expression of a custom panel of genes was measured in esophageal biopsies. Immunohistochemical staining of biopsies was performed. Among children with EoE, 32% (8\/25) had PPI-R EoE. ATP12A, ATP4A, tryptase-beta 2 (TPSB2), CLC and IL13 had higher expression in PPI-NR EoE compared to PPI-R EoE or controls. Immunohistochemical staining of ATP12A was higher among PPI-R EoE and PPI-NR EoE, compared to non-EoE controls. In this study, PPI-NR EoE had significantly higher baseline gene expression of mast cell, cytokine, proton pump, and eosinophil genes compared to PPI-R EoE. PPIs may be involved in an inflammatory cascade of mast cell activation that stimulates IL-13 release, which upregulates ATP12A and ATP4A that leads to eosinophil recruitment. Histologic PPI failure may occur when increased gene expression of these components is high and cannot be overcome pharmacologically, especially in the case of proton pump genes.<\/jats:p>","DOI":"10.1093\/dote\/doae071","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T01:40:19Z","timestamp":1725586819000},"source":"Crossref","is-referenced-by-count":2,"title":["Increased expression of proton pump and allergic inflammation genes predicts PPI failure in pediatric eosinophilic esophagitis"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1106-8206","authenticated-orcid":false,"given":"Paroma","family":"Bose","sequence":"first","affiliation":[{"name":"Department of Pediatrics , Division of Pediatric Gastroenterology, Hepatology, and Nutrition, , Indianapolis, IN,","place":["USA"]},{"name":"Indiana University School of Medicine\/Riley Hospital for Children , Division of Pediatric Gastroenterology, Hepatology, and Nutrition, , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenwu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pegah","family":"Mehrpouya-Bahrami","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN,","place":["USA"]},{"name":"Labcorp Biomarker Solution Center , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina","family":"Collins","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Laboratory Medicine, Indiana University School of Medicine , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony M","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Albright","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Laboratory Medicine, Indiana University School of Medicine , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muhammad T","family":"Idrees","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology and Laboratory Medicine, Indiana University School of Medicine , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Health Data Science, Indiana University School of Medicine , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep K","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Division of Pediatric Gastroenterology, Hepatology, and Nutrition, , Indianapolis, IN,","place":["USA"]},{"name":"Indiana University School of Medicine\/Riley Hospital for Children , Division of Pediatric Gastroenterology, Hepatology, and Nutrition, , Indianapolis, IN,","place":["USA"]},{"name":"Division of Pediatric Gastroenterology , Hepatology, and Nutrition, , Birmingham, AL,","place":["USA"]},{"name":"The University of Alabama at Birmingham , Hepatology, and Nutrition, , Birmingham, AL,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily C","family":"Hon","sequence":"additional","affiliation":[{"name":"Department of Pediatrics , Division of Pediatric Gastroenterology, Hepatology, and Nutrition, , Indianapolis, IN,","place":["USA"]},{"name":"Indiana University School of Medicine\/Riley Hospital for Children , Division of Pediatric Gastroenterology, Hepatology, and Nutrition, , Indianapolis, IN,","place":["USA"]},{"name":"Medical Gastroenterology, Eli Lilly and Company , Indianapolis, IN,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark H","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Indiana University School of Medicine , Indianapolis, 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