循环α-1抗胰蛋白酶及其C端肽可区分细菌性与病毒性社区获得性肺炎
Circulating alpha-1 antitrypsin and its c-terminal peptides differentiate bacterial from viral community-acquired pneumonia.
摘要(中文译文)
区分细菌性与病毒性社区获得性肺炎（CAP）仍是重大临床挑战，常导致不恰当的抗菌药物使用。α-1抗胰蛋白酶（AAT）是一种急性期蛋白，可调节中性粒细胞蛋白酶活性，并在炎症过程中被切割，生成生物活性肽。我们研究了循环AAT及其肽段能否区分细菌性与病毒性CAP。血清样本来自81例前瞻性入组的CAP成人患者（细菌性，n=36；病毒性，n=45），分别于入院时（第0天）和第3天采集。采用ELISA测定AAT浓度，采用LC-MS/MS定量9种AAT来源的C端肽段。采用多变量logistic回归和受试者工作特征（ROC）分析评估其与CAP病因的关联。细菌性CAP的AAT浓度在入院时（p=0.006）和第3天（p<0.001）均显著高于病毒性CAP，且在调整临床协变量后仍与细菌性病因独立相关，而C反应蛋白（CRP）则不然。结合AAT、年龄和白细胞计数的预测模型显示出最高的区分效能（AUC=0.803）。分析的9种肽段中有4种（C36、C37、C40和C42）可稳定检出。细菌性CAP入院时C37水平较高（p=0.010）。C36呈现相似趋势，但从第0天至第3天下降（p=0.006）。相反，病毒性CAP中C40水平升高（p=0.017），导致入院时C40/AAT比值高于细菌性CAP（p=0.014）。在细菌性CAP中观察到AAT、肽段与炎症标志物之间的相关性，而病毒性CAP中未观察到，提示AAT加工模式不同。循环AAT可独立区分细菌性与病毒性CAP，且与年龄和白细胞计数联合时，其区分效能优于基于CRP的模型。AAT来源肽段的不同模式提示病因特异性的蛋白水解加工，值得进一步评估其作为区分细菌性与病毒性CAP标志物的价值。
Abstract
Distinguishing bacterial from viral community-acquired pneumonia (CAP) remains a major clinical challenge, often leading to inappropriate antimicrobial use. Alpha-1 antitrypsin (AAT) is an acute-phase protein that regulates neutrophil protease activity and is cleaved during inflammation, generating bioactive peptides. We investigated whether circulating AAT and its peptides could discriminate bacterial from viral CAP. Serum samples were obtained from 81 prospectively enrolled adults with CAP (bacterial, n = 36; viral, n = 45) at hospital admission (day 0) and day 3. AAT concentrations were measured by ELISA, and nine AAT-derived C-terminal peptides were quantified by LC-MS/MS. Associations with CAP etiology were assessed using multivariable logistic regression and receiver operating characteristic (ROC) analyses. AAT concentrations were significantly higher in bacterial than viral CAP at both admission (p = 0.006) and day 3 (p < 0.001) and remained independently associated with bacterial etiology after adjustment for clinical covariates, whereas C-reactive protein (CRP) did not. A predictive model combining AAT, age, and leukocyte count demonstrated the highest discriminatory performance (AUC = 0.803). Four of nine analyzed peptides (C36, C37, C40, and C42) were consistently detectable. C37 levels were higher in bacterial CAP at admission (p = 0.010). C36 showed a similar trend but declined from day 0 to day 3 (p = 0.006). In contrast, C40 levels increased in viral CAP (p = 0.017), resulting in a higher C40/AAT ratio at admission compared with bacterial CAP (p = 0.014). Correlations between AAT, peptides, and inflammatory markers were observed in bacterial but not in viral CAP, indicating distinct patterns of AAT processing. Circulating AAT independently discriminates bacterial from viral CAP and, when combined with age and leukocyte count, show improved discriminatory performance compared with CRP-based models. Distinct patterns of AAT-derived peptides suggest etiology-specific proteolytic processing and merit further evaluation as markers for differentiating bacterial and viral CAP.
如何引用
AMA
Milad Pashai Fakhri, Friedemann R Börner, Julia Held, Kokilavani Sivaraman, Jan Fuge, Jan Rupp, et al. Circulating alpha-1 antitrypsin and its c-terminal peptides differentiate bacterial from viral community-acquired pneumonia.. Journal of translational medicine. 2026; doi:10.1186/s12967-026-08651-8.
APA
Milad Pashai Fakhri, Friedemann R Börner, Julia Held, Kokilavani Sivaraman, Jan Fuge, Jan Rupp, et al (2026). Circulating alpha-1 antitrypsin and its c-terminal peptides differentiate bacterial from viral community-acquired pneumonia.. Journal of translational medicine. https://doi.org/10.1186/s12967-026-08651-8
GB/T 7714
Milad Pashai Fakhri, Friedemann R Börner, Julia Held, Kokilavani Sivaraman, Jan Fuge, Jan Rupp, et al. Circulating alpha-1 antitrypsin and its c-terminal peptides differentiate bacterial from viral community-acquired pneumonia.[J]. Journal of translational medicine, 2026 doi:10.1186/s12967-026-08651-8.
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