Neutrophil CD64, sTREM-1, and mHLA-DR as diagnostic and prognostic biomarkers in pediatric community-acquired pneumonia

Background Traditional biomarkers like C-reactive protein (CRP) have limited diagnostic and prognostic utility in pediatric community-acquired pneumonia (CAP). This hospital-based case–control study evaluated non-classic immune biomarkers—neutrophil CD64 (nCD64), soluble Triggering Receptor Expressed on Myeloid cells-1 (sTREM-1), and monocyte HLA-DR (mHLA-DR) for CAP diagnosis and outcome prediction. Methods We enrolled 120 children (24–60 months): 60 with CAP and 60 age/sex-matched healthy controls. Primary endpoints were diagnostic accuracy (CAP vs. controls) and associations with disease severity (Clinical Respiratory Score), hospitalization duration, ICU admission, mechanical ventilation, and mortality. Plasma sTREM-1 was measured by ELISA; nCD64 and mHLA-DR expression by flow cytometry. Results sTREM-1, nCD64, and nCD64/lymphocyte ratio were significantly higher, while mHLA-DR was lower in CAP cases versus controls (all p < 0.001). All biomarkers correlated significantly with CRP (r = 0.724, 0.760, 0.687, and -0.369, respectively; p < 0.001). Levels increased stepwise with disease severity and adverse outcomes. The nCD64/lymphocyte ratio showed superior diagnostic accuracy (AUC 0.97, 95% CI 0.93–0.99; 90% sensitivity, 99% specificity), outperforming CRP (AUC 0.89, 95% CI 0.82–0.94). Deceased children ( n = 4, 6.7%) exhibited the most pronounced biomarker alterations. Conclusion The nCD64/lymphocyte ratio is a highly accurate diagnostic biomarker for pediatric CAP. nCD64, sTREM-1, and mHLA-DR demonstrate significant prognostic value, effectively stratifying severity and predicting outcomes. Integrating these biomarkers may enhance clinical management and antibiotic stewardship.