Potential asthma biomarkers identified by nontargeted proteomics of extracellular vesicles in exhaled breath condensate

被引：0

作者：

Hara, Reina ^{[1
]}

Takeda, Yoshito ^{[1
]}

Enomoto, Takatoshi ^{[1
]}

Yoshimura, Hanako ^{[1
]}

Yamamoto, Makoto ^{[1
]}

Tanizaki, Satoshi ^{[1
]}

Shirai, Yuya ^{[1
]}

Kawasaki, Takahiro ^{[1
]}

Nakayama, Mana ^{[1
]}

Amiya, Saori ^{[1
]}

Adachi, Yuichi ^{[1
]}

Noda, Yoshimi ^{[1
]}

Niitsu, Takayuki ^{[1
]}

Edahiro, Ryuya ^{[1
]}

Yaga, Moto ^{[1
]}

Hosono, Yuki ^{[1
]}

Naito, Maiko ^{[1
]}

Masuhiro, Kentaro ^{[1
]}

Naito, Yujiro ^{[1
]}

Shiroyama, Takayuki ^{[1
]}

Miyake, Kotaro ^{[1
]}

Fukushima, Kiyoharu ^{[1
]}

Koyama, Shohei ^{[1
]}

Iwahori, Kota ^{[1
]}

Hirata, Haruhiko ^{[1
]}

Nagatomo, Izumi ^{[1
]}

Kawashima, Yusuke ^{[2
]}

Nogami-Itoh, Mari ^{[3
]}

Kumanogoh, Atsushi ^{[1
,4
,5
,6
,7
,8
,9
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Resp Med & Clin Immunol, 2-2 Yamada Oka, Suita, Osaka, Japan

[2] Kazusa DNA Res Inst, Dept Appl Genom, Kisarazu, Japan

[3] Osaka Univ, Cpd Lib Screening Ctr, Grad Sch Pharmacol Sci, Suita, Japan

[4] Osaka Univ, Immunol Frontier Res Ctr, Dept Immunopathol, Suita, Japan

[5] Osaka Univ, Ctr Adv Modal, Suita, Japan

[6] Osaka Univ, DDS, Suita, Japan

[7] Osaka Univ, Ctr Infect Dis Educ & Res, Suita, Suita, Japan

[8] Osaka Univ, Inst Open & Transdisciplinary Res Initiat, Integrated Frontier Res Med Sci Div, Suita, Japan

[9] Osaka Univ, Japan Agcy Med Res & Dev Core Res Evolut Sci & Tec, Suita, Japan

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY: GLOBAL | 2025年 / 4卷 / 02期

基金：

日本学术振兴会;

关键词：

Exhaled breath condensate; proteomics; bioinformatics; biomarker; exosome; extracellular vesicles; bronchial asthma; COPD; phenotype; endotype; EXPRESSION; MICRORNAS;

D O I：

10.1016/j.jacig.2025.100432

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

Background: Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are often misdiagnosed or undiagnosed, highlighting the need for more noninvasive and accessible diagnostic tools. Although exhaled breath condensate (EBC) is recognized as a biomarker resource for respiratory diseases, nontargeted proteomics of extracellular vesicles (EVs) in EBC has not been explored. Objective: Our aim was to identify protein signatures in EBCderived EVs (EBC-EVs) and potential biomarkers for BA and COPD. Methods: EBC-EVs were isolated from 8 patients with BA, 5 patients with COPD, and 9 healthy controls by using the phosphatidylserine affinity method. The isolated EBC-EVs were analyzed by using data-independent acquisition proteomics to identify differentially expressed proteins (DEPs) and their associations with clinical parameters. Results: Overall, 2524 proteins were identified. In the patients with BA, 20 proteins were upregulated, and 34 were downregulated. In the patients with COPD, 46 proteins were upregulated and 67 were downregulated. Although the enriched pathways and protein networks showed similarities between BA and COPD, they also indicated distinct pathophysiologic differences. In all, 5 BA-DEPs and 2 COPD-DEPs correlated with clinical parameters. For BA, S100 calcium-binding protein P levels were inversely correlated with FEV1 value, and ribosomal protein S10 levels were inversely correlated with blood eosinophil count. Clathrin heavy chain 2 correlated with serum IgE levels. For COPD, 14-3-3 protein theta and galectin-related protein showed positive and negative correlations with FEV1 value, respectively. Conclusions: Proteomics of EBC-EVs has enabled the identification of potential diagnostic biomarkers for BA and COPD. "Breathomics"of EBC-EVs offers a promising noninvasive approach for diagnosis and phenotyping of respiratory diseases. (J Allergy Clin Immunol Global 2025;4:100432.)

引用

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