Michels Erik H A, Peters-Sengers Hessel, de Brabander Justin, Schuurman Alex R, Reijnders Tom D Y, Haak Bastiaan W, Brands Xanthe, Joosten Sebastiaan C M, Faber Daniël R, Cremer Olaf L, Douma Renée A, de Vos Alex F, Wiersinga W Joost, Butler Joe M, van der Poll Tom
Center for Infection and Molecular Medicine and.
Department of Epidemiology and Data Science, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Am J Respir Crit Care Med. 2025 Nov;211(11):2180-2190. doi: 10.1164/rccm.202502-0325OC.
Community-acquired pneumonia (CAP) represents a significant health burden. We aimed to map the plasma proteome in patients with CAP and associate protein abundance with pathophysiology, tissue source, and outcome. We measured the plasma proteome of patients with CAP upon admission to a general ward using Olink technology (derivation cohort). Additional Olink measurements were performed in patients with CAP admitted to the ICU and patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia across care settings (validation cohorts). Of 2,676 proteins analyzed in 93 ward patients with CAP and 21 healthy control subjects, 904 (33.8%) were higher in CAP, 396 (14.8%) lower, and 1,376 (51.4%) not different. More abundant proteins were associated with innate immune and mitosis pathways and mainly originated from lung and cardiac tissue. A total of 131 proteins associated with time to clinical stability (TCS), of which 124 (primarily related to monocyte and macrophage and RNA processing) were connected with a long TCS. Most TCS-associated proteins were differentially abundant in nonsurvivors versus survivors among 88 patients with ICU-CAP (1.4- to 3.5-fold higher) and 305 patients with SARS-CoV-2 pneumonia (1.16- to 1.35-fold lower or 1.14- to 2.65-fold higher; all < 0.05). In the general population (UK Biobank), 115 of 124 (92.7%) proteins correlated with long TCS were associated with an increased risk of pneumonia during a 10-year follow-up, whereas 6 of 7 (85.7%) proteins correlated with shorter TCS were associated with a lower risk of pneumonia. This now publicly available CAP plasma proteome provides information on pathophysiological mechanisms and tissue involvement and may support development of personalized therapies.
社区获得性肺炎（CAP）是一项重大的健康负担。我们旨在绘制CAP患者的血浆蛋白质组图谱，并将蛋白质丰度与病理生理学、组织来源和预后相关联。我们使用Olink技术测量了入住普通病房的CAP患者的血浆蛋白质组（推导队列）。在入住ICU的CAP患者和不同护理环境下的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）肺炎患者中进行了额外的Olink测量（验证队列）。在93名病房CAP患者和21名健康对照受试者中分析的2676种蛋白质中，904种（33.8%）在CAP中较高，396种（14.8%）较低，1376种（51.4%）无差异。丰度较高的蛋白质与先天免疫和有丝分裂途径相关，主要源自肺和心脏组织。共有131种蛋白质与临床稳定时间（TCS）相关，其中124种（主要与单核细胞、巨噬细胞和RNA加工有关）与较长的TCS相关。在88名ICU-CAP患者（高1.4至3.5倍）和305名SARS-CoV-2肺炎患者（低1.16至1.35倍或高1.14至2.65倍；均<0.05）中，大多数与TCS相关的蛋白质在非幸存者和幸存者之间存在差异丰度。在普通人群（英国生物银行）中，124种与较长TCS相关的蛋白质中有115种（92.7%）在10年随访期间与肺炎风险增加相关，而7种与较短TCS相关的蛋白质中有6种（85.7%）与肺炎风险较低相关。这个现已公开的CAP血浆蛋白质组提供了有关病理生理机制和组织受累的信息，并可能支持个性化治疗的开发。
