Host Serum Biomarker Signatures in Mycobacteriologically Cured Pulmonary Tuberculosis Patients with Persistent Lung Inflammation on 18F-FDG PET/CT

TL;DR

This study identifies serum biomarkers linked to persistent lung inflammation in TB patients who have completed treatment, which could help diagnose lingering inflammation and prevent long-term lung damage.

Contribution

The study identifies serum biomarkers associated with persistent lung inflammation in TB patients post-treatment, offering potential diagnostic tools.

Findings

15 serum biomarkers were significantly elevated in patients with extensive lung inflammation.

14 biomarkers showed potential as diagnostic markers with AUC values between 0.707 and 0.806.

13 biomarkers correlated with total lung glycolysis (TLG) values, supporting their clinical utility.

Abstract

Background: Pulmonary inflammation is a widely recognized characteristic of active tuberculosis (TB). Although standard TB treatment is effective, a substantial proportion of mycobacteriologically cured TB patients experience persistent pulmonary inflammation, which can lead to long-term lung impairment, post-tuberculosis lung disease (PTLD) and potentially TB recurrence. Methods: We conducted a case–control study to compare host serum biomarker profiles in individuals with minimal (TLG < 50 SUVbw*mL, n = 37) versus extensive (TLG ≥ 50 SUVbw*mL, n = 34) persistent lung inflammation following completion of standard drug-sensitive TB treatment. Lung inflammation was measured by 18F-FDG PET/CT scan using total lung glycolysis (TLG) as a surrogate marker. All participants had negative sputum cultures at four months of TB treatment, and blood samples were collected at treatment completion (month six). A Luminex® multiplex assay performed on the Bio-Plex® 200 platform was used to analyze 48 host serum biomarkers involved in cytokine/chemokine signaling. Results: Following multiple t-test analysis, fifteen biomarkers were significantly elevated (p < 0.05) in participants with extensive persistent lung inflammation compared to those with minimal inflammation. Among these, 14 demonstrated potential as discriminatory markers, with area under the curve (AUC) values ranging from 0.707 to 0.806, sensitivities ranging from 47.06% to 73.53%, and specificities ranging from 70.27% to 83.78%. Notably, 13 of these 16 candidate biomarkers significantly correlated with TLG values, further supporting their potential clinical utility. Conclusion: We report associations between serum inflammatory mediators and persistent pulmonary inflammation following mycobacterial clearance in TB patients, highlighting their potential as diagnostic biomarkers that could potentially meet the target product profile (TPP) criteria.

Figures