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

Suzuki, M., Cole, J. J., Konno, S., Makita, H., Kimura, H., Nishimura, M. and Maciewicz, R. A. (2021) Large‐scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma. Clinical and Translational Allergy, 11(10), e12091. (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®), 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.

• Item Type: Articles
• Additional Information: he Hokkaido COPD cohort study was supported by a scientific research grant from the Ministry of Education, Science, Culture and Sports of Japan (17390239 and 2139053 to Masaharu Nishimura), Boehringer Ingelheim, Pfizer, and a grant to the Respiratory Failure Research Group from the Ministry of Health, Labor, and Welfare, Japan. The Hi-CARAT study was supported by the Ministry of Education, Science, Culture, and Sports of Japan scientific Research Grants (21390253 and 24249049 to Masaharu Nishimura), the Japan Allergy Foundation, AstraZeneca, KYORIN Pharmaceutical, and a grant to the Respiratory Failure Research Group from the Ministry of Health, Labor, and Welfare, Japan.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cole, Mr John and Maciewicz, Dr Rose

Creator Roles

Cole, J. J.: Data curation, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing
Maciewicz, R. A.: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review and editing

• Authors: Suzuki, M., Cole, J. J., Konno, S., Makita, H., Kimura, H., Nishimura, M., and Maciewicz, R. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Clinical and Translational Allergy
• Publisher: Wiley
• ISSN: 2045-7022
• ISSN (Online): 2045-7022
• Published Online: 20 December 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Clinical and Translational Allergy 11(10): e12091
• Publisher Policy: Reproduced under a Creative Commons License