S100A8/A9 as a biomarker for differentiating pulmonary tuberculosis from community-acquired pneumonia in children: a multicenter cohort study in China

Background Differentiating pulmonary tuberculosis (PTB) from community-acquired pneumonia (CAP) in children remains a significant diagnostic challenge. This study aimed to evaluate the diagnostic value of serum S100A8/A9 in pediatric populations. Methods This multicenter prospective study enrolled 1,629 children aged 0∼≤ 18 years with definitive diagnostic classifications, including a discovery cohort ( n = 1,092) and a validation cohort ( n = 537). Participants were stratified into three groups: PTB (Confirmed, Unconfirmed), CAP (Viral, Bacterial, Mycoplasma pneumoniae , Mixed), and healthy controls (HC). Serum S100A8/A9 levels were quantified by enzyme-linked immunosorbent assay, and diagnostic performance was assessed using ROC analysis. Results In both cohorts, S100A8/A9 levels were markedly lower in PTB than in CAP but higher than in healthy controls. (both p < 0.001). For distinguishing PTB from CAP, S100A8/A9 achieved AUC values of 0.916 (95% CI: 0.895-0.937, sensitivity 87.1%, specificity 81.8%) in the discovery cohort and 0.932 (95% CI: 0.906–0.958, sensitivity 87.5%, specificity 86.4%) in the validation cohort. Compared with all CAP etiological subgroups, PTB children had the lowest S100A8/A9 levels, with the highest AUC of 0.954 for PTB vs. Mycoplasma pneumoniae CAP. Age-stratified analysis revealed excellent discriminatory performance in children aged 5-18 years (AUC = 0.955 for PTB versus overall CAP). but impaired in children under 5 years (AUC = 0.838 for PTB versus overall CAP), with lower sensitivity (57.4%) for discriminating PTB from Viral-CAP. Furthermore, a concentration-dependent distribution was observed, with higher S100A8/A9 levels associated with a decreasing proportion of PTB and an increasing proportion of CAP. In children aged 5–18 years, levels < 1,000 ng/mL were predominantly PTB (92.1%), and levels > 1,900 ng/mL were highly predictive of CAP (96.8%). Conclusions Serum S100A8/A9 is a promising potential biomarker for distinguishing pediatric PTB from CAP, characterized by age-related distribution and concentration-dependent diagnostic pattern.