Abstract

At present, diagnosis for neurosyphilis remains a major clinical challenge. Venereal Disease Research Laboratory (VDRL) titer of the cerebrospinal fluid (CSF) is suboptimally sensitive to diagnose neurosyphilis, which can be negative in neurosyphilis patients, especially in asymptomatic neurosyphilis patients. In the search for biomarkers of neurosyphilis, we investigated the chemokine profile in CSF of neurosyphilis patients and found that the concentrations of CXCL13, CXCL10 and CXCL8 were selectively elevated in neurosyphilis patients and correlated with CSF protein concentration and CSF-VDRL titer. After antibiotic treatment, the concentration of these chemokines was dramatically reduced. The area under the ROC curve (AUC) of CSF CXCL13, CXCL8,CXCL10 and the CSF/serum ratio of CXCL13, CXCL8,CXCL10 in the diagnosis of neurosyphilis were 0.940, 0.899, 0.915, 0.963, 0.846 and 0.926, respectively. The corresponding sensitivities/specificities of CSF CXCL13, CXCL8,CXCL10 and the CSF/serum ratio of CXCL13, CXCL8,CXCL10 in diagnosis of neurosyphilis were 85.4%/89.1%, 79%/90.1% and 79.6%/91.1%, 86.6%/99%, 79%/73.3% and 86%/92.1%, respectively. Our results suggest that the elevated concentrations of CXCL13, CXCL8, and CXCL10 or their increasing CSF/serum ratios may be potential biomarkers of neurosyphilis, particularly for asymptomatic neurosyphilis. Reduced concentration of these chemokines may indicate the prognosis of antibiotic therapy.

Highlights

  • Chemokines and their receptors are expressed in both neuronal and glial cells of the CNS

  • The levels of cerebrospinal fluid (CSF) CXCL13, CXCL8 and CXCL10 were selectively elevated in neurosyphilis patients by chemokine antibody array

  • The CSF CXCL13, CXCL10 and CXCL8 levels were significantly higher in neurosyphilis patients than those in non-neurosyphilis patients

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Summary

Introduction

Chemokines and their receptors are expressed in both neuronal and glial cells of the CNS. Elevated levels of various chemokines have been found in CSF and been associated with the severity or progression of several CNS inflammatory disorders[6,7,8]. Previous studies have shown that the concentration of CSF CXCL13 was significantly elevated and had added value for the diagnosis of neurosyphilis in HIV co-infected syphilis patients, suggesting that chemokines may be involved in the inflammatory disorder of CNS in neurosyphilis patients[11,12,13]. We analyzed the global expression profiles of 36 chemokines in CSF of neurosyphilis patients for the purpose of screening novel biomarkers as a diagnosis of neurosyphilis in HIV-negative syphilis patients, especially in asymptomatic neurosyphilis patients

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