Comparative Plasma Proteomics of Drug-Susceptible and Multidrug-Resistant Tuberculosis: Identifying Novel Biomarker Signatures in North East Nigeria

The biochemical distinction between drug-susceptible and multidrug-resistant tuberculosis has critical implications for treatment selection, yet proteomic differences between these phenotypes in the Nigerian patient population remain entirely uncharacterised. This study applies discovery and targeted plasma proteomics to identify biomarker signatures that differentiate drug-susceptible TB from MDR-TB in patients in Borno and Adamawa States, North East Nigeria. A case-control design was employed, recruiting 60 drug-susceptible TB patients, 60 phenotypically confirmed MDR-TB patients, and 60 healthy community contacts. Plasma proteomics was performed by sequential window acquisition of all theoretical mass spectra on a TripleTOF 6600 mass spectrometer. Differential protein expression was analysed by MSstats, and pathway enrichment by Ingenuity Pathway Analysis identified dysregulated networks. Candidate biomarkers, including complement components, acute phase reactants, and tissue remodelling proteins, were validated in an independent cohort by targeted multiple reaction monitoring with isotope-labelled standards. A clinical prediction model integrating proteomic and routine biochemical data was developed using random forest classification. This research constitutes an original contribution to TB biomarker science in an African high-burden context and proposes a novel proteomic framework for MDR-TB phenotyping. Keywords: plasma proteomics, multidrug-resistant tuberculosis, biomarkers, mass spectrometry, North East Nigeria.