副结核
亚临床感染
急性期蛋白
发病机制
脂质代谢
病态的
折叠变化
蛋白质组学
生物
生物标志物
病理
医学
内科学
免疫学
分枝杆菌
下调和上调
生物化学
炎症
基因
肺结核
作者
Alejandra Isabel Navarro León,Marta Muñoz,Natàlia Iglesias,Cristina Blanco‐Vázquez,Ana Balseiro,Fátima Milhano Santos,Sergio Ciordia,Fernando J. Corrales,Tania Iglesias,Rosa Casáis
标识
DOI:10.1021/acs.jproteome.3c00244
摘要
The lack of sensitive diagnostic methods to detect Mycobacterium avium subsp. paratuberculosis (Map) subclinical infections has hindered the control of paratuberculosis (PTB). The serum proteomic profiles of naturally infected cows presenting focal and diffuse pathological forms of PTB and negative controls (n = 4 per group) were analyzed using TMT-6plex quantitative proteomics. Focal and diffuse are the most frequent pathological forms in subclinical and clinical stages of PTB, respectively. One (focal versus (vs.) control), eight (diffuse vs. control), and four (focal vs. diffuse) differentially abundant (DA) proteins (q-value < 0.05) were identified. Ingenuity pathway analysis of the DA proteins revealed changes in the acute-phase response and lipid metabolism. Six candidate biomarkers were selected for further validation by specific ELISA using serum from animals with focal, multifocal, and diffuse PTB-associated lesions (n = 108) and controls (n = 56). Overall, the trends of the serum expression levels of the selected proteins were consistent with the proteomic results. Alpha-1-acid glycoprotein (ORM1)-based ELISA, insulin-like growth factor-binding protein 2 (IGFBP2)-based ELISA, and the anti-Map ELISA had the best diagnostic performance for detection of animals with focal, multifocal, and diffuse lesions, respectively. Our findings identify potential biomarkers that improve diagnostic sensitivity of PTB and help to elucidate the mechanisms involved in PTB pathogenesis.
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