WS10.02Proteomic analysis of nasal lavage fluid and sputum samples in people with cystic fibrosis during 24 months of treatment with elexecaftor/tezacaftor/ivacaftor - The RECOVER study

IF 5.4 2区医学 Q1 RESPIRATORY SYSTEM

Journal of Cystic Fibrosis Pub Date : 2025-06-01 DOI:10.1016/j.jcf.2025.03.547

S. Nolan , S. Weldon , R. Cregan , B. Elnazir , M. Williamson , D. Cox , B. Linane , E. McKone , A. Reid , J. Davies , P. McNally , D. Downey , C. Taggart

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引用次数: 0

Abstract

Objectives

Elexecaftor/Tezacaftor/Ivacaftor (ETI) has been shown to modulate the microbial and inflammatory microenvironment in the airways of people with CF. ETI treatment is associated with a markedly reduced sputum production in many people, prompting the need for a surrogate sample type to allow measurement of indices of infection and inflammation. We sought to characterise the changes in the sputum and nasal lavage fluid (NLF) proteome in PwCF in response to ETI and determine the similarity of the responses in both sample types.

Methods

124 PwCF over 12y/o were recruited to the study and samples were collected prior to treatment and at subsequent visits up to 2 years. 26 sputum samples and 111 nasal lavage samples underwent proteomic analysis. Significant differences in protein enrichment were calculated and pathway analysis performed.

Results

Principal component analysis revealed differences in the proteome of patient sputum before and after treatment, with little clustering in NLF samples. Differential enrichment analysis of sputum prior to and after treatment showed significant pathway enrichment of over 700 proteins - complement cascade proteins (p<0.001) and peptidase inhibitors (p<0.001) with decreases in proteins involved in the regulation of pathogen clearance (p<0.001). Differential analysis of NLF samples in the same fashion revealed 117 significantly different proteins, with pathway enrichment for regulators of proteases and the antimicrobial response (p<0.001). 31 proteins were found to be significantly enriched and 9 decreased in NLF and sputum.

Conclusions

ETI treatment is associated with differential expression of proteins involved in immune responses, particularly the complement cascade and proteins implicated in the protease-antiprotease imbalance. Sputum samples displayed very clear distinctions in proteome profiles before and after treatment, unlike NLF samples. NLF and sputum proteomes displayed limited similarity.

查看原文本刊更多论文

囊性纤维化患者使用elexaftor /tezacaftor/ivacaftor治疗24个月期间鼻灌洗液和痰样本的蛋白质组学分析——RECOVER研究

目的elexexaftor /Tezacaftor/Ivacaftor （ETI）已被证明可以调节CF患者气道中的微生物和炎症微环境。ETI治疗与许多人的痰产量显着减少有关，这促使需要替代样品类型来测量感染和炎症指标。我们试图描述PwCF对ETI反应中痰液和鼻灌洗液（NLF）蛋白质组的变化特征，并确定两种样品类型反应的相似性。方法招募124例12y/o以上的PwCF患者，在治疗前和随访2年时收集样本。26份痰液样本和111份鼻灌洗液样本进行了蛋白质组学分析。计算了蛋白质富集的显著差异，并进行了途径分析。结果主成分分析结果显示，治疗前后患者痰蛋白组存在差异，且NLF样本中聚类性较小。治疗前后痰液的差异富集分析显示，超过700种蛋白质的通路富集——补体级联蛋白（p<0.001）和肽酶抑制剂（p<0.001），而参与调节病原体清除的蛋白质减少（p<0.001）。以同样的方式对NLF样本进行差异分析，发现117种显著不同的蛋白质，蛋白酶调节因子和抗菌反应的途径富集（p<0.001）。NLF和痰液中有31种蛋白显著富集，9种蛋白显著降低。结论seti治疗与免疫应答相关蛋白的差异表达有关，特别是补体级联蛋白和蛋白酶-抗蛋白酶失衡相关蛋白。与NLF样本不同，痰样本在治疗前后的蛋白质组谱显示出非常明显的差异。NLF和痰蛋白组显示有限的相似性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cystic Fibrosis 医学-呼吸系统

CiteScore

10.10

自引率

13.50%

发文量

1361

审稿时长

50 days

期刊介绍： The Journal of Cystic Fibrosis is the official journal of the European Cystic Fibrosis Society. The journal is devoted to promoting the research and treatment of cystic fibrosis. To this end the journal publishes original scientific articles, editorials, case reports, short communications and other information relevant to cystic fibrosis. The journal also publishes news and articles concerning the activities and policies of the ECFS as well as those of other societies related the ECFS.