一种新型piRNA与高T2型哮喘表型相关
2023/12/20
摘要
背景：Piwi相互作用RNA（piRNA），作为最大的非编码RNA群，调节转录过程。目前尚不清楚piRNA是否与高T2型哮喘相关。
目标：我们旨在研究piRNA与儿童哮喘中的高T2表型之间的关联。
方法：我们对儿童哮喘管理计划（CAMP）中的462名受试者的血浆样本进行了测序作为研究队列，哥斯达黎加哮喘遗传研究（GACRS）中的1165名受试者作为重复队列。首先过滤测序读数，对piRNA读数进行注释和标准化。线性回归用于分析piRNA与哮喘患儿外周血嗜酸性粒细胞计数、总血清IgE水平和长期哮喘恶化的关联。进行了中介分析以调查效应方向。然后，我们确定循环piRNA是否存在于哮喘患者气道上皮细胞中，通过GEO公共数据集进行验证。
结果：在CAMP中，有15种piRNA与嗜酸性粒细胞计数显著相关（p≤0.05），其中3种在GACRS中成功复现。在CAMP中，有11种piRNA与总IgE显著关联，其中一种在GACRS中复现。所有22种显著的piRNA都在体外上皮细胞中被鉴定出来，其中6种在哮喘患者和健康对照者之间差异表达。有14种piRNA与长期哮喘发作相关，piRNA对长期哮喘发作的影响通过嗜酸性粒细胞计数和血清IgE水平进行了中介。
结论：piRNA与儿童哮喘中的外周血嗜酸性粒细胞和总血清IgE相关，并可能在高T2型哮喘中发挥重要作用。
A Novel piRNA Associates with T2-high Asthma Phenotypes
Jiang Li, Xiaoning Hong, Mingye Jiang, Alvin T Kho, Anshul Tiwari, Alberta L Wang, Robert P Chase, Juan C Celedón, Scott T Weiss, Michael J McGeachie, Kelan G Tantisira
Abstract
Background: Piwi-interacting RNA (piRNA), the largest non-coding RNA group, regulate transcriptional processes. Whether piRNAs are associated with T2-high asthma is unknown.
Objective: We sought to investigate the association between piRNAs and T2-high asthma in childhood asthma.
Methods: We sequenced plasma samples from 462 subjects in the Childhood Asthma Management Program (CAMP) as the discovery cohort and 1,165 subjects in the Genetics of Asthma in Costa Rica Study (GACRS) as a replication cohort. Sequencing reads were filtered first and piRNA reads were annotated and normalized. Linear regression was used for the association analysis of piRNAs and peripheral blood eosinophil count, total serum IgE level and long-term asthma exacerbation in children with asthma. Mediation analysis was performed to investigate the effect direction. We then ascertained if the circulating piRNAs were present in asthmatic airway epithelial cells in a GEO public dataset.
Results: Fifteen piRNAs were significantly associated with eosinophil count in CAMP (p≤0.05), and three were successfully replicated in GACRS. Eleven piRNAs were associated with total IgE in CAMP, and one of these was replicated in GACRS. All 22 significant piRNAs were identified in epithelial cells in vitro, and six of these were differentially expressed between subjects with asthma and healthy controls. Fourteen piRNAs were associated with the long-term asthma exacerbation and effect of piRNAs on the long-term asthma exacerbation are mediated through eosinophils count and serum IgE level.
Conclusion: piRNAs are associated with peripheral blood eosinophils and total serum IgE in childhood asthma and may play important roles in T2-high asthma.
背景：Piwi相互作用RNA（piRNA），作为最大的非编码RNA群，调节转录过程。目前尚不清楚piRNA是否与高T2型哮喘相关。
目标：我们旨在研究piRNA与儿童哮喘中的高T2表型之间的关联。
方法：我们对儿童哮喘管理计划（CAMP）中的462名受试者的血浆样本进行了测序作为研究队列，哥斯达黎加哮喘遗传研究（GACRS）中的1165名受试者作为重复队列。首先过滤测序读数，对piRNA读数进行注释和标准化。线性回归用于分析piRNA与哮喘患儿外周血嗜酸性粒细胞计数、总血清IgE水平和长期哮喘恶化的关联。进行了中介分析以调查效应方向。然后，我们确定循环piRNA是否存在于哮喘患者气道上皮细胞中，通过GEO公共数据集进行验证。
结果：在CAMP中，有15种piRNA与嗜酸性粒细胞计数显著相关（p≤0.05），其中3种在GACRS中成功复现。在CAMP中，有11种piRNA与总IgE显著关联，其中一种在GACRS中复现。所有22种显著的piRNA都在体外上皮细胞中被鉴定出来，其中6种在哮喘患者和健康对照者之间差异表达。有14种piRNA与长期哮喘发作相关，piRNA对长期哮喘发作的影响通过嗜酸性粒细胞计数和血清IgE水平进行了中介。
结论：piRNA与儿童哮喘中的外周血嗜酸性粒细胞和总血清IgE相关，并可能在高T2型哮喘中发挥重要作用。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2023 Dec 4:S0091-6749(23)02403-X. doi: 10.1016/j.jaci.2023.10.032.)
(J Allergy Clin Immunol. 2023 Dec 4:S0091-6749(23)02403-X. doi: 10.1016/j.jaci.2023.10.032.)
A Novel piRNA Associates with T2-high Asthma Phenotypes
Jiang Li, Xiaoning Hong, Mingye Jiang, Alvin T Kho, Anshul Tiwari, Alberta L Wang, Robert P Chase, Juan C Celedón, Scott T Weiss, Michael J McGeachie, Kelan G Tantisira
Abstract
Background: Piwi-interacting RNA (piRNA), the largest non-coding RNA group, regulate transcriptional processes. Whether piRNAs are associated with T2-high asthma is unknown.
Objective: We sought to investigate the association between piRNAs and T2-high asthma in childhood asthma.
Methods: We sequenced plasma samples from 462 subjects in the Childhood Asthma Management Program (CAMP) as the discovery cohort and 1,165 subjects in the Genetics of Asthma in Costa Rica Study (GACRS) as a replication cohort. Sequencing reads were filtered first and piRNA reads were annotated and normalized. Linear regression was used for the association analysis of piRNAs and peripheral blood eosinophil count, total serum IgE level and long-term asthma exacerbation in children with asthma. Mediation analysis was performed to investigate the effect direction. We then ascertained if the circulating piRNAs were present in asthmatic airway epithelial cells in a GEO public dataset.
Results: Fifteen piRNAs were significantly associated with eosinophil count in CAMP (p≤0.05), and three were successfully replicated in GACRS. Eleven piRNAs were associated with total IgE in CAMP, and one of these was replicated in GACRS. All 22 significant piRNAs were identified in epithelial cells in vitro, and six of these were differentially expressed between subjects with asthma and healthy controls. Fourteen piRNAs were associated with the long-term asthma exacerbation and effect of piRNAs on the long-term asthma exacerbation are mediated through eosinophils count and serum IgE level.
Conclusion: piRNAs are associated with peripheral blood eosinophils and total serum IgE in childhood asthma and may play important roles in T2-high asthma.
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