Serum High-Mobility Group Box 1 and Disease Severity in Pulmonary Tuberculosis: A Cross-Sectional Study

Abstract

High-mobility group box 1 is released during inflammation and tissue injury, but its relationship with pulmonary tuberculosis severity remains unclear. This study evaluated its associations with Respiratory manifestations, sputum smear grade, and chest radiographic extent. This cross-sectional study consecutively recruited 92 adults with bacteriologically confirmed pulmonary tuberculosis at a tertiary referral hospital in Makassar, Indonesia, from May to June 2026. Respiratory manifestations were classified as cough alone, cough with dyspnea, cough with hemoptysis, or cough with both hemoptysis and dyspnea. Pretreatment sputum acid-fast bacilli smears were graded as 1+, 2+, or 3+, and chest radiographic disease was classified as minimal or extensive. Serum high-mobility group box 1 concentrations were measured using a quantitative sandwich enzyme-linked immunosorbent assay. Data were analyzed using the Kruskal–Wallis test with Bonferroni-adjusted pairwise comparisons, the independent-samples t test, Spearman’s rank correlation, and multiple linear regression. Serum high-mobility group box 1 differed across Respiratory manifestation groups and sputum smear grades (both P<0.001). Sputum smear grade correlated strongly with serum concentrations (ρ=0.841, P<0.001). Concentrations were higher in extensive than minimal radiographic disease (41,708.55±7,120.62 versus 29,597.53±6,225.99 pg/mL; P<0.001). After adjustment, Respiratory manifestations and sputum smear grades 2+ and 3+ remained associated with higher concentrations, whereas radiographic extent did not. Serum high-mobility group box 1 was independently associated with Respiratory manifestations and sputum smear grade. Its association with radiographic extent was attenuated after adjustment. Further studies should assess its potential as a disease-activity biomarker.