Serum Omics Analysis Reveals Tissue Damage and Metabolic Reprogramming in Cavitary Pulmonary Tuberculosis.

Cavitary pulmonary tuberculosis (cPTB) is the most destructive manifestation of Mycobacterium tuberculosis infection and is associated with poor treatment response and high transmissibility. To capture the systemic disturbances that accompany cavity formation, we profiled sera from 30 cPTB patients, 30 noncavitary PTB patients, and 30 matched healthy volunteers using proximity-extension proteomics and untargeted ultraperformance liquid-chromatography tandem mass spectrometry. Multigroup analysis revealed broad suppression of cell-junction proteins and rewiring of amino-acid and lipid metabolism in PTB; these changes were accentuated in cPTB, where 15 cardiomyocyte-associated proteins and fifty-nine metabolites differed significantly from noncavitary PTB. Integrated network mapping converged on two consistently down-regulated molecules─desmoglein-4 (DSG4) and amyl salicylate─whose combined abundance showed moderate discrimination of cPTB from noncavitary PTB (AUC = 0.738). These findings are consistent with cavity formation being associated with perturbations in cardiovascular-related pathways and broad metabolic reprogramming, and they nominate the DSG4-amyl salicylate pair as an exploratory, hypothesis-generating signature that requires validation in independent cohorts before any clinical interpretation or host-directed therapeutic use.