CXCL13, CXCL10 and CXCL8 as Potential Biomarkers for the Diagnosis of Neurosyphilis Patients

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.

Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance

“…A combination of three chemokines was positively correlated to a high AUC value (0.949), 90.4% sensitivity, and 92.9% specificity. However, it was not markedly different from the high diagnostic significance of CXCL13 or VDRL [55]. Therefore, CXCL13 may be a good diagnostic marker in situations in which CSF-VDRL results are nonreactive [53].…”

“…The cut-off point of Q CXCL13 indicated by the authors showed 87.5% sensitivity and 69.2% specificity, which may suggest that Q CXCL13 is a good diagnostic marker to discriminate neurosyphilis from syphilis and other neurological diseases [11]. Furthermore, some studies have demonstrated that the CSF/serum ratio is significantly increased in neurosyphilis patients [12,55]. Rupprecht et al observed that in 100% of neurosyphilis patients the ratio was low (below 4), whereas in 89.5% of neuroborreliosis patients, the ratio was above the cut-off value.…”

“…Recent retrospective studies have revealed that CXCL13 levels are increased in the CSF and serum of patients with early and late neurosyphilis. Those patients were found to have higher CSF levels of the chemokine than individuals without neurological symptoms [6,[10][11][12][51][52][53][54][55][56]. Release of high levels of CXCL13 during the in vitro incubation of monocytes with Treponema pallidum may be evidence that CXCL13 could be a good diagnostic marker for nervous system infections caused by this particular spirochete [10].…”

Management of neurosyphilis: time for a new approach?

“…While these techniques, and others, appear to improve the sensitivity of existing CSF serology they are considerably more labour intensive than existing techniques and are yet to be validated or widely applied. CSF cytokine and chemokine profiling of patients with neurosyphilis has led to an expanding library of novel markers that correlate with CNS inflammatory responses and invasion of the CNS . A prospective study looking at the utility of CSF levels of chemokine CXCL 13 and T. pallidum DNA PCR to improve diagnostic accuracy in patients with suspected neurosyphilis has recently begun recruiting in Shanghai (Clinical Trials Registry number ChiCTR‐DDD‐16009591).…”

“…CSF cytokine and chemokine profiling of patients with neurosyphilis has led to an expanding library of novel markers that correlate with CNS inflammatory responses and invasion of the CNS. [18][19][20] A prospective study looking at the utility of CSF levels of chemokine CXCL 13 and T. pallidum DNA PCR to improve diagnostic accuracy in patients with suspected neurosyphilis has recently begun recruiting in Shanghai (Clinical Trials Registry number ChiCTR-DDD-16009591). Validation of these indicators will be difficult and further work is required before these tests can be confidently incorporated into any existing neurosyphilis diagnostic algorithm.…”