Nasal transcriptome differences preceding recurrent wheezing in infancy.

IF 11.4 1区 医学 Q1 ALLERGY
Poshmaal Dhar, Martin O'Hely, Luba Sominsky, Sarah Ashley, Sarath C Ranganathan, Peter D Sly, Fiona Collier, Mimi Lk Tang, Rachel Morgan, Toby Mansell, Richard Saffery, David Burgner, Anne-Louise Ponsonby, Peter Vuillermin
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Abstract

Background: Mucosal immune responses and epithelial barrier function are key emerging determinants of susceptibility to wheezing illnesses in early life.

Objective: We investigated the association between nasal transcriptome in healthy infants and the subsequent incidence of recurrent wheeze.

Methods: In a population-derived prebirth cohort study, whole transcriptome sequencing was performed to compare the nasal transcriptome at 1 month of age from 26 infants who subsequently developed recurrent wheeze (parents' record in symptom diary) in the first year of life to 22 infants who remained recurrent wheeze-free. Differentially expressed genes (DEGs) were identified using DEseq2, followed by over-representation pathway (GO and KEGG) and upstream regulator analyses (Ingenuity Pathway Analysis).

Results: 202 DEGs (false discovery rate ≤ 0.1 and absolute log2 fold change > 1; 66 upregulated and 136 downregulated) were associated with recurrent wheeze. Upregulated GO pathways associated with recurrent wheeze included chemokine-mediated signalling, eosinophil and monocyte chemotaxis. The downregulated GO included cilium organisation and cellular aldehyde metabolic process. TNF emerged as the key driver (adjusted p-value and Z-score) of DEG patterns in the recurrent wheeze group, with OSMR and IL21 identified as master regulators.

Conclusion: The nasal transcriptome in early infancy is associated with subsequent recurrent wheezes, indicating upregulation of immune cell chemotaxis, decreased epithelial barrier function, and altered cilium organisation and mitochondrial function. Future studies are required to evaluate the use of nasal transcriptome in the early detection of infants at risk of recurrent wheeze and to generate new knowledge of antecedent pathways as targets for novel primary prevention strategies.

婴儿反复喘息前的鼻转录组差异。
背景:黏膜免疫反应和上皮屏障功能是早期生活中对喘息疾病易感性的关键决定因素。目的:研究健康婴儿鼻转录组与随后复发性喘息发生率之间的关系。方法:在一项人群衍生的出生前队列研究中,进行全转录组测序,比较26名在出生后第一年出现复发性喘息(父母在症状日记中记录)的婴儿和22名没有复发性喘息的婴儿在1个月大时的鼻转录组。使用DEseq2鉴定差异表达基因(DEGs),随后使用过度表达途径(GO和KEGG)和上游调控分析(Ingenuity途径分析)。结果:202 deg(假发现率≤0.1,绝对对数2倍变化> 1;66例上调,136例下调)与复发性喘息相关。与复发性喘息相关的氧化石墨烯上调途径包括趋化因子介导的信号传导、嗜酸性粒细胞和单核细胞趋化性。下调的氧化石墨烯包括纤毛组织和细胞醛代谢过程。在复发性哮喘组中,TNF成为DEG模式的关键驱动因素(调整p值和z分数),OSMR和IL21被确定为主要调节因子。结论:婴儿早期鼻转录组与随后的反复喘息有关,表明免疫细胞趋化性上调,上皮屏障功能下降,纤毛组织和线粒体功能改变。未来的研究需要评估鼻转录组在早期发现有复发性喘息风险的婴儿中的应用,并对作为新型一级预防策略目标的先行途径产生新的认识。
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来源期刊
CiteScore
25.90
自引率
7.70%
发文量
1302
审稿时长
38 days
期刊介绍: The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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