Mitsuyama Yumi, Matsumoto Hisatake, Sugihara Fuminori, Fujimi Satoshi, Ogura Hiroshi, Oda Jun
Department of Traumatology and Acute Critical Medicine, Graduate School of Medicine, The University of Osaka, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Division of Trauma and Surgical Critical Care, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan.
J Intensive Care. 2025 May 15;13(1):26. doi: 10.1186/s40560-025-00793-z.
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.
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.
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).
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.
急性呼吸窘迫综合征（ARDS）仍然是一项重大的临床挑战，其发病机制尚未完全明确。尽管先前的研究尚未充分关注生物标志物的纵向比较，但已对ARDS患者的血浆和支气管肺泡灌洗液（BALF）进行了蛋白质组学分析，以发现诊断和预后标志物。本研究旨在阐明ARDS患者急性期和亚急性期的蛋白质组学特征，以更好地了解ARDS的病理生理进展。
这是一项针对成年ARDS患者的单中心、前瞻性观察性研究，在ARDS的急性期和亚急性期收集血浆和BALF样本，并通过质谱法鉴定和分析综合蛋白质。
从21例ARDS患者中收集了血浆和BALF，从24名健康供体中收集了血浆，分析了其中的694种血浆蛋白和2017种BALF蛋白。血浆和BALF中常见的与凝血和补体相关的过程在急性期比在亚急性期更为明显。在急性期的BALF中，与体液和免疫反应相关的途径被激活，而与伴侣蛋白和蛋白质折叠相关的过程被抑制。IPA分析显示，B细胞受体信号传导被激活得最为明显，而热休克蛋白90（HSP90）伴侣蛋白循环、蛋白质折叠以及与细胞应激反应和正确蛋白质加工相关的其他途径被抑制。最被激活的上游调节因子是干扰素γ（IFN-γ），最被抑制的是Notch受体1（NOTCH1）。
对ARDS患者急性期和亚急性期的血浆和BALF进行了蛋白质组学比较。在急性期的BALF中，主要是B细胞受体信号传导的体液免疫被激活，而HSP90循环和蛋白质折叠机制被灭活。
