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Large-scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma

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Title: Large-scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma
Authors: Suzuki, Masaru Browse this author →KAKEN DB
Cole, John J. Browse this author
Konno, Satoshi Browse this author →KAKEN DB
Makita, Hironi Browse this author →KAKEN DB
Kimura, Hiroki Browse this author →KAKEN DB
Nishimura, Masaharu Browse this author →KAKEN DB
Maciewicz, Rose A. Browse this author
Keywords: COPD
endotypes
exosome
proteomics
severe asthma
Issue Date: Dec-2021
Publisher: John Wiley & Sons
Journal Title: Clinical and Translational Allergy
Volume: 11
Issue: 10
Start Page: e12091
Publisher DOI: 10.1002/clt2.12091
Abstract: Background Chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases. Methods The plasma proteome was evaluated using an aptamer-based affinity proteomics platform (SOMAscan (R)), representing 1238 proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics. Results Subjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under-explored. Conclusion This investigational study evaluating the plasma proteome in clinically-phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups.
Type: article
URI: http://hdl.handle.net/2115/83943
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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