Prognostic value of sputum HMGB1 in smear-negative and smear-positive pulmonary TB

BACKGROUND Diagnosing pulmonary TB (PTB) in patients with negative sputum acid-fast bacillus (AFB) staining is challenging and impedes transmission control. This study assessed the prognostic utility of sputum high-mobility group box protein 1 (HMGB1) in PTB, focusing on treatment outcomes. METHODS In a prospective cohort study, we enrolled 66 PTB patients: 37 smear-positive (MTB-MC) and 29 smear-negative but clinically suspected (MTB-SN), confirmed by bacteriology or treatment response. All underwent GeneXpert MTB/RIF testing. Sputum HMGB1 levels were measured at baseline, 2 months, and 6 months post-treatment. RESULTS Of the 66 participants, 37 had bacteriologically confirmed PTB (MTB-MC) with AFB grades ranging from scanty (n = 6) to 3+ (n = 12), and 29 had smear-negative PTB (MTB-SN). Sputum HMGB1 levels declined significantly during treatment (P < 0.001). Baseline HMGB1 strongly correlated with bacillary load (r2 = 0.4645, P < 0.0001). Notably, 2-month HMGB1 levels predicted culture conversion, with an area under the curve of 0.885 for treatment failure in the MTB-MC group. CONCLUSION Sputum HMGB1 is a promising marker for monitoring treatment response and predicting failure in PTB, especially in smear-negative cases. Despite limited diagnostic specificity due to elevation in inflammatory conditions, its role in assessing 2-month culture conversion warrants further study. Larger studies are needed to validate clinical thresholds. .