Immune Biomarker Combinations for Diagnosis Monitoring of Latent Tuberculosis Infection

Abstract

Objective: Global Tuberculosis (TB) eradication efforts must also focus on detecting and treating cases of Latent TB Infection (LTBI); persons with LTBI can progress to active TB at any time, often many years or even decades after the initial infection, thereby serving as a source of new infections. Methods: The aim was evaluated the diagnostic accuracy of the combination of serological host biomarkers that may support the differentiation between LTBI and Non-Infected (NI) individuals. A total of 182 adult Warao Amerindians were included; cases with LTBI (n=103) and Non-Infected (NI) individuals (n=79). The Real-time quantitative PCR (qPCR) was performed on all peripheral blood samples from Warao Amerindians and analyzed transcriptional immune biomarkers (i.e., IFN-γ, CD14, MMP-9, CCR5, CCL11, CXCL9/MIG, and uPAR/PLAUR proteins) under stimulation condition with ESAT-6, CFP10, and TB7.7 Mycobacterium Tuberculosis (Mtb)-antigens. Additionally, Enzyme-Linked Immunosorbent Assays (ELISA) were performed for evaluating host biomarker anti-synthetic peptides (5 ESAT-6 and 17 Ag85A synthetic peptides) covering Mtb antigen sequences. Results: The approach’s diagnostic information was compared using Receiver Operating Characteristic (ROC) curves. The ROC analysis revealed high biosignature discriminative ability for the relative gene expression of MMP-9 high levels (AUC=0.799 ± 0.071: 0.640 - 0.917, 95% CI), p < 0.002) between LTBI and NI; additionally IgG anti-synthetic peptide; ESAT-6 P-12037 (AUC=0.640; 0.545-0.735 95% CI, p<0.007) allowed differentiation between LTBI and NI or healthy ones. Conclusion: The accuracy of the MMP-9/IgG anti-P-12037 combination could have a high discriminative ability for diagnosing LTBI; such an approach holds promise for further validation.