外周血单核细胞中 T2 炎症基因的转录组表达与哮喘的纵向临床结果:来自 COREA 研究的启示

IF 4.6 2区 医学 Q1 RESPIRATORY SYSTEM
Lung Pub Date : 2024-08-01 Epub Date: 2024-07-12 DOI:10.1007/s00408-024-00728-9
Duong Duc Pham, Eunsoon Shin, Jong Eun Lee, Ji-Hyang Lee, Woo-Jung Song, Hyouk-Soo Kwon, You Sook Cho, Sungho Won, Tae-Bum Kim
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引用次数: 0

摘要

背景:与临床生物标志物相比,基因表达能为哮喘患者的纵向临床结果提供独特的信息:本研究探讨了 T2 炎症通路上游细胞因子(IL-25、IL-33 和 TSLP)和下游细胞因子(IL-5、IL-4 和 IL-13)的基因表达水平与 12 个月的病情加重、肺功能和类固醇使用随访之间的关联:对 279 名成年哮喘患者的外周血单核细胞进行了转录组测序分析。采用生存分析和线性混合效应模型研究高水平和低水平基因表达组与临床结果之间的潜在差异。对上游、下游和所有 6 种细胞因子分别进行了分析:一般来说,T2 炎症细胞因子基因表达与血液中嗜酸性粒细胞计数的相关性较弱(所有 r 结论):这些研究结果表明,在 MSEA 患者中,T2 炎症通路下游细胞因子的基因表达水平可作为哮喘内分型的指标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study.

Transcriptomic Expression of T2-Inflammation Genes in Peripheral Blood Mononuclear Cells and Longitudinal Clinical Outcomes in Asthma: Insights from the COREA Study.

Background: Gene expression can provide distinct information compared to clinical biomarkers in the context of longitudinal clinical outcomes in asthma patients.

Objective: This study examined the association between the gene expression levels of upstream (IL-25, IL-33, and TSLP) and downstream cytokines (IL-5, IL-4, and IL-13) in the T2 inflammatory pathway with a 12-month follow-up of exacerbation, lung function, and steroid use.

Methods: Transcriptomic sequencing analysis was performed on peripheral blood mononuclear cells from 279 adult asthmatics. Survival analysis and linear mixed-effect models were used to investigate potential differences between the high-level and low-level gene expression groups and the clinical outcomes. Analysis was performed separately for the upstream, downstream, and all 6 cytokines.

Results: In general, T2 inflammatory cytokine gene expression showed a weak correlation with blood eosinophil counts (all r < 0.1) and clinical outcomes. Among moderate-to-severe eosinophilic asthma (MSEA) patients, individuals with elevated levels of downstream cytokines were at increased risk of time-to-first exacerbation (p = 0.044) and a greater increase of inhaled corticosteroid use over time (p = 0.002) compared to those with lower gene expression. There was no association between baseline T2 inflammatory cytokine gene expression and the longitudinal changes in lung function over time among MSEA patients.

Conclusion: These findings suggest that, among MSEA patients, the gene expression levels of downstream cytokines in the T2 inflammatory pathway may serve as indicators for endotyping asthma.

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来源期刊
Lung
Lung 医学-呼吸系统
CiteScore
9.10
自引率
10.00%
发文量
95
审稿时长
6-12 weeks
期刊介绍: Lung publishes original articles, reviews and editorials on all aspects of the healthy and diseased lungs, of the airways, and of breathing. Epidemiological, clinical, pathophysiological, biochemical, and pharmacological studies fall within the scope of the journal. Case reports, short communications and technical notes can be accepted if they are of particular interest.
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