Jacobse Justin, Brown Rachel, Revetta Frank, Vaezi Michael, Buendia Matthew A, Williams Christopher S, Higginbotham Tina, Washington M Kay, Goettel Jeremy, Hiremath Girish, Choksi Yash A
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands; Division of Molecular Pathogenesis, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tenn; Veterans Affairs Tennessee Valley Health Care System, Nashville, Tenn.
Medical Scientist Training Program, Vanderbilt University School of Medicine, Nashville, Tenn; Program in Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tenn.
J Allergy Clin Immunol. 2024 Mar;153(3):759-771. doi: 10.1016/j.jaci.2023.10.002. Epub 2023 Oct 17.
Eosinophilic esophagitis (EoE) is a chronic immune mediated inflammatory disorder of the esophagus. It is still unknown why children and adults present differently, and there is little evidence about why it is more common in men than women.
Our aim was to synthesize published and unpublished esophageal bulk RNA-sequencing (RNA-seq) data to gain novel insights into the pathobiology of EoE and examine the differences in EoE transcriptome by sex and age group.
Esophageal bulk RNA-seq data from 5 published and 2 unpublished studies resulting in 137 subjects (EoE: N = 76; controls: N = 61) were analyzed. For overall analysis, combined RNA-seq data of patients with EoE were compared with those of controls and subgroup analysis was conducted in patients with EoE by age of the patient (children [<18 years] vs adults [≥18 years]) and sex (female vs male). Gene-set enrichment analysis, ingenuity pathway analysis (IPA), cell-type analysis, immunohistochemistry, and T-cell or B-cell receptor analysis were performed.
Overall analysis identified dysregulation of new genes in EoE compared with controls. IPA revealed that EoE is characterized by a mixed inflammatory response compared with controls. Cell-type analysis showed that cell composition varied with age: children had more mast cells, whereas adults had more macrophages. Finally, gene-set enrichment analysis and IPA revealed pathways that were differentially regulated in adults versus children and male versus female patients with EoE.
Using a unique approach to analyze bulk RNA-seq data, we found that EoE is characterized by a mixed inflammatory response, and the EoE transcriptome may be influenced by age and sex. These findings enhance insights into the molecular mechanisms of EoE.
嗜酸性食管炎（EoE）是一种慢性免疫介导的食管炎症性疾病。儿童和成人为何表现不同仍不清楚，且关于为何男性比女性更常见的证据很少。
我们的目的是综合已发表和未发表的食管全转录组RNA测序（RNA-seq）数据，以深入了解EoE的病理生物学，并研究EoE转录组在性别和年龄组中的差异。
分析了来自5项已发表和2项未发表研究的食管全转录组RNA-seq数据，共137名受试者（EoE：N = 76；对照组：N = 61）。进行总体分析时，将EoE患者的合并RNA-seq数据与对照组的数据进行比较，并按患者年龄（儿童[<18岁]与成人[≥18岁]）和性别（女性与男性）对EoE患者进行亚组分析。进行了基因集富集分析、 Ingenuity通路分析（IPA）、细胞类型分析、免疫组织化学以及T细胞或B细胞受体分析。
总体分析发现，与对照组相比，EoE中有新基因的失调。IPA显示，与对照组相比，EoE的特征是混合性炎症反应。细胞类型分析表明，细胞组成随年龄而变化：儿童有更多的肥大细胞，而成人有更多的巨噬细胞。最后，基因集富集分析和IPA揭示了EoE成年患者与儿童患者以及男性患者与女性患者之间差异调节的通路。
通过一种独特的方法分析全转录组RNA-seq数据，我们发现EoE的特征是混合性炎症反应，且EoE转录组可能受年龄和性别的影响。这些发现增强了对EoE分子机制的认识。
