Proteomic profiling of cerebrospinal fluid reveals pathophysiology changes and diversity of treatment response in pediatric streptococcus pneumoniae meningitis

Streptococcus pneumoniae meningitis (SPM) is a critical pediatric infection with a high mortality rate. This study aimed to investigate changes in the cerebrospinal fluid (CSF) proteome in SPM patients and identify biomarkers for SPM diagnosis and treatment monitoring. Here, we retrospectively collected and evaluated CSF proteomes of 47 SPM and 116 non-CNS-infected patients (Control), including longitudinal samples from 11 SPM patients. Candidate biomarkers were validated by parallel reaction monitoring (PRM) in 146 samples (36 longitudinal/12 SPM, 110 Control) and evaluated via receiver operating characteristic (ROC) analysis. We identified 648 differentially expressed proteins (DEPs) associated with complement activation and oxidative stress. SPM patients with abnormal CSF white blood cells (SPMAN) exhibited dysregulation in coagulation and fibrinolysis, while those with normal counts (SPMN) displayed redox homeostasis alterations. The ELANE and H4C1 panel achieved a superior diagnostic accuracy (AUC = 0.967), and the combination of IGKV1-17, IGKC, and IGKV4-1 effectively tracked therapy response (AUC = 0.872). This study establishes CSF proteomic signatures of pediatric SPM, providing dual-purpose biomarker panels for clinical diagnosis and treatment monitoring, with implications for targeted interventions.