Analysis of Treponema pallidum DNA and CXCL13 in Cerebrospinal Fluid in HIV-Negative Syphilis Patients

Abstract

Neurosyphilis (NS) is a chronic infectious disease associated with Treponema pallidum subsp. pallidum (TP) infection of the central nervous system. The purpose of this study was to offer evidence for the diagnosis and treatment of NS by revealing the detection of TP DNA and CXCL13 concentration in the cerebrospinal fluid (CSF) of HIV-negative syphilis patients. Patients and Methods: This study included 75 syphilis patients. The frequency of TP invasion into the CSF was detected by nested PCR. ELISA was performed to detect CSF CXCL13 concentrations, and ROC analysis was performed to assess diagnostic accuracy. Sociodemographic data, clinical symptoms, and laboratory indices of patients were collected. CSF CXCL13 levels and clinical characteristics of syphilis patients were investigated retrospectively. Results: The detection rate of CSF DNA of TP by nested PCR was 5.3% and 16.7% in HIV-negative syphilis patients and NS patients, respectively. There was a significant difference between the NS and non-NS groups in terms of neurological symptoms, CSF TPPA, CSF TRUST, CSF nucleated cells, CSF protein, and CSF CXCL13 levels (P<0.05). ROC curve analysis showed that the AUC for CSF CXCL13 levels was 0.906 (95% CI 0.832-0.981, P <0.0001), with an optimal critical value of 57.85 pg/mL and sensitivity and specificity of 88.89% and 78.95%, respectively. Conclusion: Nested PCR can be used as an auxiliary diagnosis of NS, and CSF CXCL13 >60 pg/mL has high sensitivity and specificity for NS patients and non-NS patients. CXCL13 may be a useful marker to distinguish NS from non-NS syphilis in HIVnegative patients.

Towards a refined understanding of cerebrospinal fluid CXCL13 in neurosyphilis diagnosis among people with HIV

“…Similarly, our findings align with previous research that identified a CSF CXCL13 cutoff of at least 76.3 pg/ml for neurosyphilis diagnosis in PWH [6], and a recent prospective study on 75 syphilis patients without HIV, employing nested PCR for definitive neurosyphilis diagnosis, determined a 57.85 pg/ml cutoff for CSF CXCL13 through ROC curve analysis [12].…”

“…It is true that the co-occurrence of neurosyphilis or of neuroborreliosis [11] with all the above is infrequent; however, other confounding conditions can be more prevalent. For example, EBV DNA is detectable in the CSF of up to 20% of asymptomatic PWH [12]. As shown in Fig.…”

“…1b, among virally suppressed PWH, even low-level replication of EBV in the CSF (min-max 31-893 DNA copies/ml) was associated with significantly higher levels of CSF CXCL13. Interestingly, both CSF CXCL13 and CSF anti-EBV IgG have been associated with the cognitive performance of PWH [4,12].…”

Cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis in people with HIV

“…This is further corroborated by a recent study of 75 syphilis patients without HIV, which determined a CSF CXCL13 cutoff of 57.85 pg/mL, indicating that the influence of HIV on CSF CXCL13 levels may be minimal. The consistency of CSF CXCL13 as a biomarker across patients with and without HIV reinforces its reliability for neurosyphilis diagnosis [33].…”

Diagnostic value of cerebrospinal fluid chemokine c-x-c motif ligand 13 for neurosyphilis: A systematic review and meta-analysis

“…Finally, 6 articles were included in this meta-analysis. [19][20][21][22][23][24] The primary characteristics of 6 articles are summarized in Table 1. There were 720 syphilis and 338 neurosyphilis individuals involved in this meta-analysis.…”