Do Mast Cells Reduce Response to Proton Pump Inhibitors in Pediatric Eosinophilic Esophagitis?
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY(2022)
摘要
Treatment response to proton pump inhibitors (PPIs) in eosinophilic esophagitis (EoE) remains poorly understood. We examined mast cell burden in esophageal biopsies of pediatric subjects with PPI-responsive (PPI-R) EoE, PPI-nonresponsive (PPI-NR) EoE, and non-EoE esophageal dysfunction (controls). Subjects undergoing diagnostic endoscopy for esophageal dysfunction were enrolled. Subjects with EoE, defined as ≥ 15 eosinophils/high powered field (hpf) on esophageal biopsy, were treated with 8 weeks of PPI therapy followed by repeat endoscopy. Subjects with < 15 eosinophils/hpf had PPI-R EoE and ≥ 15 eosinophils/hpf had PPI-NR EoE. Gene expression in esophageal biopsies in subject samples was determined using the Nanostring nCounter® Analysis System or RT-qPCR. Biopsies were immunostained with anti-CD117 (mean count/10 hpf). Of 72 subjects enrolled, 41 met criteria for EoE and 25 had follow-up endoscopy after PPI therapy. Eight had PPI-R EoE and 17 had PPI-NR EoE. Tryptase-beta-2 (TPSB2) and carboxypeptidase-3 (CPA3), enzymes involved in mast cell activation, were differentially expressed among PPI-R EoE, PPI-NR EoE, and controls. TPSB2 and CPA3 median gene expression was highest in PPI-NR EoE compared to PPI-R EoE and controls [H(3)=18.17, p=0.0001 and H(3)=13.06, p=0.0015 respectively]. CD117 counts were significantly higher in EoE compared to controls [6.5±6.4 vs 1.1±2.5 (p<0.001)] but did not differ between PPI-R and PPI-NR EoE [3.0±2.4 vs 4.7±4.5 (p=0.535)]. Though subjects with PPI-NR EoE had high expression of TPSB2 and CPA3 genes compared to PPI-R EoE, CD117 counts did not differ between PPI-R and PPI-NR EoE. This suggests differences in mast cell activation but not numbers among EoE endotypes.
更多查看译文
关键词
pediatric eosinophilic esophagitis,mast cells,proton pump inhibitors
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要