Heparin-Binding Protein in Cerebrospinal Fluid as a Biomarker for Bacterial Meningitis: A Study of Diagnostic Accuracy

Abstract

Objective

We aimed to evaluate the diagnostic accuracy of heparin-binding protein (HBP) in cerebrospinal fluid for the diagnosis of bacterial meningitis in patients with a suspected central nervous system infection.

Methods

This prospective multicenter cohort study determined the diagnostic accuracy of HBP in cerebrospinal fluid (CSF) for bacterial meningitis among a cohort of consecutive patients with a suspected central nervous infection. The final clinical diagnosis was considered the reference standard. The results were validated in a separate cohort.

Results

A total of 631 Dutch patients were evaluated for the current study, of which 73 (12%) had a final diagnosis of bacterial meningitis. For the differentiation of bacterial meningitis from all other disorders, diagnostic accuracy was high with an area under the curve (AUC) of 0.98 (95% confidence interval [CI] 0.96–1.00). With the proposed cutoff of 5.2 ng/ml, sensitivity was 97% with a specificity of 96%. In the population of patients with a CSF leukocyte count of 5-1,000/mm³, the AUC was 0.96 (95% CI 0.87–1.00), outperforming CSF leukocytes (AUC 0.88 [95% CI 0.79–0.97]). Combining HBP with CSF C-reactive protein (CRP) significantly increased accuracy in this population and reached a 100% sensitivity (AUC 1.00 [95% CI 0.99–1.00], cutoff 0.07, sensitivity 100%, specificity 96%). These results remained robust in an external validation cohort of 120 Danish patients (AUC 0.97 [95% CI 0.93–1.00]).

Interpretation

HBP can correctly distinguish bacterial meningitis from other disorders. It can be of additional value to current diagnostics in cases where CSF leukocyte count is relatively low, particularly when combined with CSF CRP. ANN NEUROL 2025;97:1088–1095