Neutrophil-associated Proteins as Novel Biomarkers Elevated in Cerebrospinal Fluid of Neurosyphilis Patients

Abstract

Background: The immunopathological mechanisms underlying neurosyphilis remain incompletely elucidated, and the diagnosis of neurosyphilis presents challenges.

Methods: We used an antibody microarray to detect 640 proteins in cerebrospinal fluid (CSF) samples collected from 6 non-neurosyphilis and 10 neurosyphilis patients. The levels of CSF CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 in 46 non-neurosyphilis, 51 untreated neurosyphilis, and 31 post-treatment neurosyphilis patients were quantified using enzyme-linked immunosorbent assay. The associations between the levels of these proteins and clinical parameters in neurosyphilis were evaluated using Spearman's analysis, and the diagnostic performance of these proteins in neurosyphilis was assessed using receiver operating characteristic curve.

Results: A total of 102 differentially expressed proteins between neurosyphilis and non-neurosyphilis were identified. The levels of significantly elevated neutrophil-associated proteins (CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9) in neurosyphilis were positive correlations with WBC counts, RPR titer, and protein concentration in CSF. The combination of CSF CXCL8, MMP9, and LCN2 yielded an AUC of 0.92 for diagnosing neurosyphilis, surpassing that of CSF RPR.

Conclusions: CXCL1, CXCL8, G-CSF, LCN2, MMP8, and MMP9 could be associated with central nervous system damage of neurosyphilis. The combination of CSF CXCL8, MMP9, and LCN2 is a promising biomarker for diagnosing neurosyphilis.

Keywords: Antibody microarray; Biomarker; Neurosyphilis; Neutrophil-associated proteins.