Morrison Holly A, Hoyt Kacie J, Mounzer Christina, Ivester Hannah M, Barnes Barrett H, Sauer Bryan, McGowan Emily C, Allen Irving C
Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Graduate Program in Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, VA, United States.
Front Allergy. 2023 Aug 24;4:1239273. doi: 10.3389/falgy.2023.1239273. eCollection 2023.
Eosinophilic Esophagitis (EoE) is a chronic allergic disease characterized by progressive inflammation of the esophageal mucosa. This chronic inflammatory disorder affects up to 50 per 100,000 individuals in the United States and Europe yet is limited in treatment options. While the transcriptome of EoE has been reported, few studies have examined the genetics among a cohort including both adult and pediatric EoE populations. To identify potentially overlooked biomarkers in EoE esophageal biopsies that may be promising targets for diagnostic and therapeutic development.
We used microarray analysis to interrogate gene expression using esophageal biopsies from EoE and Control subjects with a wide age distribution. Analysis of differential gene expression (DEGs) and prediction of impaired pathways was compared using conventional transcriptome analysis (TAC) and artificial intelligence-based (ADVAITA) programs. Principal Components Analysis revealed samples cluster by disease status (EoE and Control) irrespective of clinical features like sex, age, and disease severity.
Global transcriptomic analysis revealed differential expression of several genes previously reported in EoE (). In addition, we identified differential expression of several genes from the and families, which have been limited in previous reports.
Our findings suggest that there is epithelial dysregulation demonstrated by DEGs that may contribute to impaired barrier integrity and loss of epidermal cell differentiation in EoE patients. These findings present two new gene families, and , that are differentially expressed in both adult and pediatric EoE patients, which presents an opportunity for a future therapeutic target that would be useful in a large demographic of patients.
嗜酸性粒细胞性食管炎（EoE）是一种慢性过敏性疾病，其特征为食管黏膜进行性炎症。这种慢性炎症性疾病在美国和欧洲每10万人中影响多达50人，但治疗选择有限。虽然已有关于EoE转录组的报道，但很少有研究在包括成人和儿童EoE患者群体的队列中研究遗传学。以识别EoE食管活检中可能被忽视的潜在生物标志物，这些生物标志物可能是诊断和治疗开发的有前景的靶点。
我们使用微阵列分析，通过来自年龄分布广泛的EoE患者和对照受试者的食管活检来询问基因表达。使用传统转录组分析（TAC）和基于人工智能的（ADVAITA）程序比较差异基因表达（DEG）分析和受损途径预测。主成分分析显示样本按疾病状态（EoE和对照）聚类，而与性别、年龄和疾病严重程度等临床特征无关。
全转录组分析揭示了先前在EoE中报道的几个基因的差异表达（）。此外，我们鉴定了来自和家族的几个基因的差异表达，这些在先前的报道中较少涉及。
我们的研究结果表明，DEG显示存在上皮细胞失调，这可能导致EoE患者的屏障完整性受损和表皮细胞分化丧失。这些发现呈现了两个新的基因家族，和，它们在成人和儿童EoE患者中均有差异表达，这为未来的治疗靶点提供了机会，对大量患者群体将是有用的。
