Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS

Abstract Background Acute respiratory distress syndrome (ARDS) remains a significant clinical challenge, and its pathogenesis is not fully understood. Proteomic analyses of plasma and bronchoalveolar lavage fluid (BALF) in patients with ARDS have been performed to uncover diagnostic and prognostic m...

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Main Authors: Yumi Mitsuyama, Hisatake Matsumoto, Fuminori Sugihara, Satoshi Fujimi, Hiroshi Ogura, Jun Oda
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Journal of Intensive Care
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Online Access:https://doi.org/10.1186/s40560-025-00793-z
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author Yumi Mitsuyama
Hisatake Matsumoto
Fuminori Sugihara
Satoshi Fujimi
Hiroshi Ogura
Jun Oda
author_facet Yumi Mitsuyama
Hisatake Matsumoto
Fuminori Sugihara
Satoshi Fujimi
Hiroshi Ogura
Jun Oda
author_sort Yumi Mitsuyama
collection DOAJ
description Abstract Background Acute respiratory distress syndrome (ARDS) remains a significant clinical challenge, and its pathogenesis is not fully understood. Proteomic analyses of plasma and bronchoalveolar lavage fluid (BALF) in patients with ARDS have been performed to uncover diagnostic and prognostic markers, although previous studies have not adequately focused on longitudinal comparison of biomarkers. This study aimed to elucidate the proteomic profiles of patients with ARDS in the acute and subacute phases to better understand the pathophysiological progression of ARDS. Methods This was a single-center, prospective, observational study of adult patients with ARDS in whom plasma and BALF samples were collected in the acute and subacute phases of ARDS and comprehensive proteins were identified and analyzed by mass spectrometry. Results Plasma and BALF were collected from 21 ARDS patients and plasma from 24 healthy donors, from which 694 plasma proteins and 2017 BALF proteins were analyzed. Processes related to coagulation and complement commonly activated in plasma and BALF were more pronounced in the acute phase than in the subacute phase. In BALF in the acute phase, pathways related to humoral and immune responses were activated, whereas processes related to chaperones and protein folding were suppressed. IPA analysis showed that B cell receptor signaling was most activated, whereas heat shock protein 90 (HSP90) chaperone cycle, protein folding, and other pathways associated with cellular stress responses and proper protein processing were suppressed. The most activated upstream regulator was interferon gamma (IFN-γ) and the most suppressed was notch receptor 1 (NOTCH1). Conclusions The proteomics of plasma and BALF from patients with ARDS were compared in both the acute and subacute phases. In BALF in the acute phase, humoral immunity, mainly B-cell receptor signaling, was activated, whereas the HSP90 cycle and protein folding mechanisms were inactivated.
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spelling doaj-art-09ac8a6d51e942a8be7f4a591cee8b222025-08-20T03:53:58ZengBMCJournal of Intensive Care2052-04922025-05-0113111310.1186/s40560-025-00793-zLongitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDSYumi Mitsuyama0Hisatake Matsumoto1Fuminori Sugihara2Satoshi Fujimi3Hiroshi Ogura4Jun Oda5Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, The University of OsakaDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, The University of OsakaDivision of Immunology, Department of Future Medical Sciences, Kobe University Graduate School of MedicineDivision of Trauma and Surgical Critical Care, Osaka General Medical CenterDepartment of Clinical Laboratory, Osaka General Medical CenterDepartment of Traumatology and Acute Critical Medicine, Graduate School of Medicine, The University of OsakaAbstract Background Acute respiratory distress syndrome (ARDS) remains a significant clinical challenge, and its pathogenesis is not fully understood. Proteomic analyses of plasma and bronchoalveolar lavage fluid (BALF) in patients with ARDS have been performed to uncover diagnostic and prognostic markers, although previous studies have not adequately focused on longitudinal comparison of biomarkers. This study aimed to elucidate the proteomic profiles of patients with ARDS in the acute and subacute phases to better understand the pathophysiological progression of ARDS. Methods This was a single-center, prospective, observational study of adult patients with ARDS in whom plasma and BALF samples were collected in the acute and subacute phases of ARDS and comprehensive proteins were identified and analyzed by mass spectrometry. Results Plasma and BALF were collected from 21 ARDS patients and plasma from 24 healthy donors, from which 694 plasma proteins and 2017 BALF proteins were analyzed. Processes related to coagulation and complement commonly activated in plasma and BALF were more pronounced in the acute phase than in the subacute phase. In BALF in the acute phase, pathways related to humoral and immune responses were activated, whereas processes related to chaperones and protein folding were suppressed. IPA analysis showed that B cell receptor signaling was most activated, whereas heat shock protein 90 (HSP90) chaperone cycle, protein folding, and other pathways associated with cellular stress responses and proper protein processing were suppressed. The most activated upstream regulator was interferon gamma (IFN-γ) and the most suppressed was notch receptor 1 (NOTCH1). Conclusions The proteomics of plasma and BALF from patients with ARDS were compared in both the acute and subacute phases. In BALF in the acute phase, humoral immunity, mainly B-cell receptor signaling, was activated, whereas the HSP90 cycle and protein folding mechanisms were inactivated.https://doi.org/10.1186/s40560-025-00793-zARDSProteomicsMass spectrometryBALFPlasma
spellingShingle Yumi Mitsuyama
Hisatake Matsumoto
Fuminori Sugihara
Satoshi Fujimi
Hiroshi Ogura
Jun Oda
Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS
Journal of Intensive Care
ARDS
Proteomics
Mass spectrometry
BALF
Plasma
title Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS
title_full Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS
title_fullStr Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS
title_full_unstemmed Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS
title_short Longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ARDS
title_sort longitudinal proteomic analysis of pathophysiology in plasma and bronchoalveolar lavage fluid of patients with ards
topic ARDS
Proteomics
Mass spectrometry
BALF
Plasma
url https://doi.org/10.1186/s40560-025-00793-z
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