Identification of inflammatory protein biomarkers for predicting the different subtype of adult with tuberculosis: an Olink proteomic study

Objective The objective of this study was to identif y the potential inflammatory molecular biomarkers that could be utilized for early prediction of different subtype of tuberculosis (TB) in adults. Methods Plasma samples were obtained from a cohort of adults diagnosed with 48 cases of active tuberculosis ( TB), including drug susceptible TB (DS-TB, n=28), multidrug resistant TB (MDR-TB, n=20), latent TB infection (LTBI, n=20), as well as a control group of healthy individuals without any infection (HC, n=20). The expression level of 92 inflammatory-related proteins was detecte d by using the high-throughput OLINK proteomics platform. Results There were 47 inflammatory proteins showing significant difference (p<0.05) among TB, LTBI and control healthy group, and 7 of them differed significantly between HC and LTBI groups, 46 proteins differed significantly between HC and TB groups, 43 proteins differed significantly between LTBI and TB groups, and overall CXCL10 and TGF-alpha proteins differed significantly among the three groups which could be used as potential diagnostic biomarkers. Furthermore, SCF demonstrates remarkable discriminatory power in distinguishing TB from LTBI, with an area under the curve (AUC) score of 0.920. It was revealed that IL-2RB possesses significant predictive value for MDR-TB, achieving an AUC of 0.709, while CXCL9 (AUC = 0.843) and IFN-alpha (AUC=0.843) show promising diagnostic value in discriminating between active TB and healthy controls. Particularly noteworthy is the emergence of SLAMF1 as the most effective predictor for differentiating between negative and positive tuberculosis cases, with an AUC of 0.779. Additionally, IL6 exhibits a high predictive value for distinguishing between non-severe and severe pulmonary TB, achieving an AUC of 0.92. Correlation analyses revealed both positive and negative relationships among co differentiated proteins, such as a strong positive correlation between TGF-alpha and CXCL10 in LTBI versus HC. Additionally, a strong positive correlation was observed for CXCL10 and CXCL9, as well as TNF and CCL3 in non-severe versus severe pulmonary TB, alongside a negative correlation for IL-6 and SCF. These co-differentiated proteins were found to be enriched in various biological processes and molecular functions related to immune regulation and signaling pathways, such as the p53 signaling pathway, the TNF signaling pathway, and NF-kappa B signaling pathway, highlighting the complex interplay of these proteins in the immune response to TB infection. Conclusion Inflammation-related proteins were differentially expressed in adults with TB compared with controls or LTBI. The co-differentiated proteins are intercorrelated, which is involve the pathogenesis of TB via regulation of immune response and immune cell proliferation and apoptosis and phosphorylation. The integration of these proteins offers enhanced diagnostic capabilities for various subtypes of TB in adults.