Abstract
OBJECTIVE: This study aimed to characterize the plasma lipidomic profile of patients with pulmonary tuberculosis (PTB), identify lipid species with potential diagnostic utility, and explore their associations with clinical parameters to inform future biomarker development and mechanistic understanding. METHODS: In a case-control study, 50 newly diagnosed PTB patients and 50 age- and sex-matched healthy controls (HC) were enrolled between April and June 2021. Plasma samples were analyzed using LC-MS/MS-based lipidomics. Multivariate modeling and univariate statistical analyses were performed to identify differential lipid species. Receiver-operating characteristic (ROC) curves evaluated diagnostic performance, and correlation analyses assessed associations with clinical indicators. RESULTS: A total of 633 lipid species were profiled, with 61 showing significant differential expression between PTB and HC groups. When compared with controls, PTB patients exhibited significantly lower plasma levels of total cholesterol, triglycerides, HDL, and LDL (all P < 0.05), as well as reduced triacylglycerol (TAG), ceramide (CER), and hexosylceramide (HCER). In contrast, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) levels were elevated in PTB. ROC analysis identified several lipid species-particularly CER(24:0) H, HCER(d18:0/22:0) H, and PE(18:1/18:1)-with strong discriminative power (AUC > 0.75). Correlation analysis revealed weak-to-moderate associations of select lipids with age and glucose, but minimal or no correlation with BMI, sex, or smoking, indicating that lipidomic alterations are primarily disease-driven. CONCLUSION: PTB patients display a distinct plasma lipidomic signature, marked by disrupted glycerolipid and sphingolipid metabolism. These findings support the diagnostic value of lipidomic profiling and provide insights into PTB-associated metabolic disturbances, laying a foundation for future biomarker validation and therapeutic exploration.