儿童和青少年哮喘患者鼻上皮基因表达和总IgE
2023/10/25
摘要
背景：关于青少年鼻上皮基因表达和总IgE知之甚少。
方法：我们对469名参加波多黎各表观遗传变异和儿童哮喘(EVA-PR)研究的9-20岁波多黎各人的总IgE进行了转录组全关联研究(TWAS)，分别在所有受试者和哮喘患者中进行。然后，我们尝试使用来自三个队列的数据来重复每个分析的主要发现。在EVA-PR中，benjamin - hochberg (BH)校正P <0.05，且在≥1个复制队列中，相同方向的相关性P <0.05的基因被认为是差异表达基因(DEGs)。使用共表达分析将哮喘患者中IgE的DEGs进一步分解为基因模块，并使用公开的单细胞RNA测序数据将这些模块映射到气道上皮中的特定细胞类型。
结果：哮喘患者总IgE的DEGs数(n= 1179 DEGs)高于所有受试者(n=631 DEGs)。在哮喘患者中，DEGs被定位到11个基因模块。与总IgE正相关的顶部模块映射到下气道上皮的肌上皮细胞和粘液分泌细胞，并受IL-4、IL- 5、IL-13和IL-33的调节。在该模块中，hub基因包括CDH26、FETUB、NTRK2、CCBL1、CST1和CST2。此外，富集分析显示基因在突触发生、IL-13和铁死亡信号通路中过度表达，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：我们对鼻上皮基因表达的研究结果支持了哮喘青少年总IgE的神经免疫共调节。
Nasal epithelial gene expression and total IgE in children and adolescents with asthma.
Xu Z, Forno E, Sun Y
Abstrast
Background: Little is known about nasal epithelial gene expression and total IgE in youth.
Methods: We conducted a transcriptome-wide association study (TWAS) of total IgE in 469 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Rico (EVA-PR) study, separately in all subjects and in those with asthma. We then attempted to replicate top findings for each analysis using data from three cohorts. Genes with Benjamini-Hochberg (BH)-adjusted P <0.05 in EVA-PR and P <0.05 in the same direction of association in ≥1 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 was identified in subjects with asthma (n=1,179 DEGs) than in all subjects (n=631 DEGs). In subjects with asthma, DEGs were mapped to eleven 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. Further, an enrichment analysis showed over-representation of genes in signalling pathways for synaptogenesis, IL-13, and ferroptosis, supporting interactions between interleukin- and acetylcholine-induced responses.
Conclusions: Our findings for nasal epithelial gene expression support neuro-immune 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知之甚少。
方法：我们对469名参加波多黎各表观遗传变异和儿童哮喘(EVA-PR)研究的9-20岁波多黎各人的总IgE进行了转录组全关联研究(TWAS)，分别在所有受试者和哮喘患者中进行。然后，我们尝试使用来自三个队列的数据来重复每个分析的主要发现。在EVA-PR中，benjamin - hochberg (BH)校正P <0.05，且在≥1个复制队列中，相同方向的相关性P <0.05的基因被认为是差异表达基因(DEGs)。使用共表达分析将哮喘患者中IgE的DEGs进一步分解为基因模块，并使用公开的单细胞RNA测序数据将这些模块映射到气道上皮中的特定细胞类型。
结果：哮喘患者总IgE的DEGs数(n= 1179 DEGs)高于所有受试者(n=631 DEGs)。在哮喘患者中，DEGs被定位到11个基因模块。与总IgE正相关的顶部模块映射到下气道上皮的肌上皮细胞和粘液分泌细胞，并受IL-4、IL- 5、IL-13和IL-33的调节。在该模块中，hub基因包括CDH26、FETUB、NTRK2、CCBL1、CST1和CST2。此外，富集分析显示基因在突触发生、IL-13和铁死亡信号通路中过度表达，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：我们对鼻上皮基因表达的研究结果支持了哮喘青少年总IgE的神经免疫共调节。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(J Allergy Clin Immunol 2023 Sep 22;doi: 10.1016/j.jaci.2023.09.014. IF: 10.228。)
(J Allergy Clin Immunol 2023 Sep 22;doi: 10.1016/j.jaci.2023.09.014. IF: 10.228。)
Nasal epithelial gene expression and total IgE in children and adolescents with asthma.
Xu Z, Forno E, Sun Y
Abstrast
Background: Little is known about nasal epithelial gene expression and total IgE in youth.
Methods: We conducted a transcriptome-wide association study (TWAS) of total IgE in 469 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Rico (EVA-PR) study, separately in all subjects and in those with asthma. We then attempted to replicate top findings for each analysis using data from three cohorts. Genes with Benjamini-Hochberg (BH)-adjusted P <0.05 in EVA-PR and P <0.05 in the same direction of association in ≥1 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 was identified in subjects with asthma (n=1,179 DEGs) than in all subjects (n=631 DEGs). In subjects with asthma, DEGs were mapped to eleven 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. Further, an enrichment analysis showed over-representation of genes in signalling pathways for synaptogenesis, IL-13, and ferroptosis, supporting interactions between interleukin- and acetylcholine-induced responses.
Conclusions: Our findings for nasal epithelial gene expression support neuro-immune coregulation of total IgE in youth with asthma.
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支气管高反应性在合并哮喘样症状的阻塞性睡眠呼吸暂停患者中的作用
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支气管扩张剂反应性与哮喘控制不佳患者的哮喘控制或症状负担无关
