Comprehensive plasma proteomic profiling reveals biomarkers for active tuberculosis

Area of Science:

• Proteomics
• Infectious Diseases
• Biomarker Discovery

Background:

• Tuberculosis (TB) remains a leading cause of infectious disease mortality worldwide.
• There is a critical need for improved diagnostic tests to identify active TB cases.
• Novel plasma-based biomarkers are sought for non-invasive TB detection.

Purpose of the Study:

• To discover and validate novel protein biomarkers in non-depleted plasma for active tuberculosis (TB).
• To establish a comprehensive TB plasma proteome profile.
• To assess the diagnostic potential of identified biomarkers.

Main Methods:

• Quantitative proteomics using multidimensional liquid chromatography and high-resolution mass spectrometry on plasma from TB patients and healthy controls.
• Discovery methodology applied to 11 active TB patients versus 10 healthy controls.
• Candidate biomarker verification in independent UK (n=118) and South African (n=203) cohorts.

Main Results:

• Generated the most extensive TB plasma proteome to date, profiling 5022 proteins.
• Identified 46 proteins with increased and 90 with decreased abundance in active TB patients.
• A five-protein panel (CFHR5, LRG1, CRP, LBP, SAA1) demonstrated significant discriminatory power (AUC = 0.81) between TB and other respiratory diseases.

Conclusions:

• Reported the most comprehensive TB plasma proteome, identifying novel candidate biomarkers.
• Verified novel markers (CFHR5, ILF2) in independent cohorts.
• Developed a five-protein biosignature with potential for improving TB diagnosis as a triage test.