儿童和青少年哮喘患者的鼻腔上皮基因表达和总 IgE。
Nasal epithelial gene expression and total IgE in children and adolescents with asthma.
机构信息
Division of Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pa; School of Medicine, Tsinghua University, Beijing, China.
Division of Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pa; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pa.
出版信息
J Allergy Clin Immunol. 2024 Jan;153(1):122-131. doi: 10.1016/j.jaci.2023.09.014. Epub 2023 Sep 22.
BACKGROUND
Little is known about nasal epithelial gene expression and total IgE in youth.
OBJECTIVE
We aimed to identify genes whose nasal epithelial expression differs by total IgE in youth, and group them into modules that could be mapped to airway epithelial cell types.
METHODS
We conducted a transcriptome-wide association study of total IgE in 469 Puerto Ricans aged 9 to 20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study, separately in all subjects and in those with asthma. We then attempted to replicate top findings for each analysis using data from 3 cohorts. Genes with a Benjamini-Hochberg-adjusted P value of less than .05 in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study and a P value of less than .05 in the same direction of association in 1 or more replication cohort were considered differentially expressed genes (DEGs). DEGs for total IgE in subjects with asthma were further dissected into gene modules using coexpression analysis, and such modules were mapped to specific cell types in airway epithelia using public single-cell RNA-sequencing data.
RESULTS
A higher number of DEGs for total IgE were identified in subjects with asthma (n = 1179 DEGs) than in all subjects (n = 631 DEGs). In subjects with asthma, DEGs were mapped to 11 gene modules. The top module for positive correlation with total IgE was mapped to myoepithelial and mucus secretory cells in lower airway epithelia and was regulated by IL-4, IL5, IL-13, and IL-33. Within this module, hub genes included CDH26, FETUB, NTRK2, CCBL1, CST1, and CST2. Furthermore, an enrichment analysis showed overrepresentation of genes in signaling pathways for synaptogenesis, IL-13, and ferroptosis, supporting interactions between interleukin- and acetylcholine-induced responses.
CONCLUSIONS
Our findings for nasal epithelial gene expression support neuroimmune coregulation of total IgE in youth with asthma.
背景
关于青少年鼻上皮基因表达和总 IgE 的信息知之甚少。
目的
我们旨在确定在年轻人中鼻上皮表达因总 IgE 而不同的基因，并将它们分为可以映射到气道上皮细胞类型的模块。
方法
我们对参与波多黎各儿童过敏性疾病研究的 469 名年龄在 9 至 20 岁的波多黎各儿童进行了全基因组关联研究，分别在所有受试者和哮喘受试者中进行了总 IgE 的全基因组关联研究。然后，我们尝试使用来自 3 个队列的数据复制每个分析的顶级发现。在波多黎各儿童过敏性疾病研究中，经 Benjamini-Hochberg 调整的 P 值小于 0.05 的基因，以及在 1 个或多个复制队列中具有相同关联方向的 P 值小于 0.05 的基因被认为是差异表达基因（DEG）。哮喘患者的总 IgE 的 DEG 进一步通过共表达分析分为基因模块，并使用公共单细胞 RNA 测序数据将此类模块映射到气道上皮的特定细胞类型。
结果
哮喘患者中鉴定出的总 IgE 的 DEG 数量（n=1179）多于所有受试者（n=631）。在哮喘患者中，DEG 被映射到 11 个基因模块。与总 IgE 呈正相关的顶级模块被映射到下气道上皮中的肌上皮细胞和黏液分泌细胞，并且受 IL-4、IL5、IL-13 和 IL-33 调节。在该模块中，核心基因包括 CDH26、FETUB、NTRK2、CCBL1、CST1 和 CST2。此外，富集分析显示，突触发生、IL-13 和铁死亡信号通路中的基因过度表达，支持白细胞介素和乙酰胆碱诱导反应之间的相互作用。
结论
我们关于鼻上皮基因表达的发现支持哮喘青少年总 IgE 的神经免疫共同调节。
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