Peripheral blood neutrophil proteomic profiling with transcriptomic data integration reveals biomarkers for tuberculosis infection diagnosis.

Background: Tuberculosis (TB) is one of the deadliest infectious diseases worldwide, causing millions of new cases and deaths annually. Rapid and accurate TB diagnostics are essential for TB control, yet current methods do not fully meet global needs. Peripheral blood neutrophils play a critical role in TB infection and represent a promising source of diagnostic markers.

Methods: We conducted a cross-sectional proteomic analysis to characterise neutrophil protein profiles in individuals with active TB (ATB), latent TB infection (LTBI), and healthy controls (HC). Stringent criteria were applied to identify differentially expressed proteins (DEPs) among these groups. Transcriptomic data were integrated to perform pathway enrichment analysis of DEPs. Three DEPs (B2M, TXN, and PRDX5) were further validated as candidate diagnostic biomarkers for Mycobacterium tuberculosis (MTB) infection using automated western blotting in a cohort of 319 individuals, including 71 ATB, 142 LTBI, and 106 HC.

Findings: Hundreds of DEPs were identified across the three groups. Integrated transcriptomic analysis revealed significant enrichment of DEPs in the NOD-like receptor signalling pathway. Receiver operating characteristic analysis of the three-protein combination (B2M, TXN, and PRDX5) yielded an area under the curve of 0.9847, with a sensitivity of 95.11% and a specificity of 96.23% for detecting MTB infection.

Interpretation: This study presents a comprehensive proteomic profile of neutrophils under different MTB infection states, and this three-protein combination may assist in the diagnosis of MTB infection.

Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2021-I2M-1-037) and the National Science and Technology Major Project of China (20212017ZX10201301-002-003).