Muir Amanda B, Ackerman Steven J, Pan Zhaoxing, Benitez Alain, Burger Cassandra, Spergel Jonathan M, Furuta Glenn T, Rothman Joshua, Wilkins Benjamin J, Arnold Michael A, Dolinsky Lauren, Grozdanovic Milica, Menard-Katcher Calies
Division of Gastroenterology, Hepatology, and Nutrition, the Children's Hospital of Philadelphia, and the Department of Pediatrics, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, Pa.
Departments of Biochemistry and Molecular Genetics, and Medicine, College of Medicine, University of Illinois at Chicago, Chicago, Ill.
J Allergy Clin Immunol. 2022 Sep;150(3):649-656.e5. doi: 10.1016/j.jaci.2022.03.022. Epub 2022 Apr 8.
Esophageal remodeling is a factor in disease progression and symptom severity for patients with eosinophilic esophagitis (EoE). Remodeling can begin early in children, resulting in stricture and food impaction. Detection of esophageal remodeling often depends on endoscopy and is appreciated only in its later stages.
We sought to determine whether luminal eosinophil-associated and remodeling proteins captured by the esophageal string test (EST) correlate with measures of esophageal remodeling and biomarkers of the epithelial-mesenchymal transition (EMT).
Patients with EoE (7-18 years old) were enrolled from 2 pediatric hospitals. Participants performed the EST and underwent endoscopy. Histology, distensibility measured by endoluminal functional lumen imaging probe, and symptoms were assessed. Protein quantitation by ELISA was performed on mucosal biopsy and EST samples. Tissue sections were evaluated for EMT. Outcome measures were summarized, and Spearman ρ was used to assess bivariate correlations.
Forty patients (68% male) were enrolled (mean age, 12.5 years). Twenty-four (60%) had active disease (≥15 eosinophils per high-power field). EST-captured eotaxin-3, major basic protein 1, EDN, eosinophil peroxidase, and Charcot-Leyden crystal protein/galectin-10 showed significant correlations with peak eosinophils per high-power field (ρ 0.53-0.68, P < .001). Luminal proteins positively correlated with endoscopic features and markers of EMT, and negatively with esophageal distensibility. Periostin was captured by the EST and correlated with eosinophil density, basal zone hyperplasia, endoscopic appearance, and markers of EMT.
Luminal markers of esophageal remodeling in addition to biomarkers of eosinophilic inflammation correlate with epithelial and functional remodeling in EoE.
食管重塑是嗜酸性食管炎（EoE）患者疾病进展和症状严重程度的一个因素。重塑可在儿童早期开始，导致狭窄和食物嵌塞。食管重塑的检测通常依赖于内镜检查，且仅在后期才能发现。
我们试图确定食管线试验（EST）捕获的管腔内嗜酸性粒细胞相关蛋白和重塑蛋白是否与食管重塑指标及上皮-间质转化（EMT）的生物标志物相关。
从两家儿科医院招募7至18岁的EoE患者。参与者进行EST并接受内镜检查。评估组织学、通过腔内功能管腔成像探头测量的扩张性以及症状。对黏膜活检和EST样本进行ELISA蛋白定量。对组织切片进行EMT评估。总结结果指标，并用Spearman ρ评估双变量相关性。
共纳入40例患者（68%为男性）（平均年龄12.5岁）。24例（60%）患有活动性疾病（每高倍视野≥15个嗜酸性粒细胞）。EST捕获的嗜酸性粒细胞趋化因子3、主要碱性蛋白1、嗜酸性粒细胞衍生神经毒素、嗜酸性粒细胞过氧化物酶以及夏科-莱登结晶蛋白/半乳糖凝集素-10与每高倍视野的嗜酸性粒细胞峰值显著相关（ρ为0.53 - 0.68，P <.001）。管腔蛋白与内镜特征和EMT标志物呈正相关，与食管扩张性呈负相关。骨膜蛋白被EST捕获，并与嗜酸性粒细胞密度、基底区增生、内镜表现及EMT标志物相关。
除嗜酸性炎症生物标志物外，食管重塑的管腔标志物与EoE中的上皮和功能重塑相关。
