Here, we assessed the regulatory response of CXCL13 in the CSF and serum of patients with neurosyphilis, syphilis and other central nervous system diseases, as well as healthy volunteers to explore the utility of CXCL13 concentrations in differentiating neurosyphilis from non-neurosyphilis/syphilis in HIV-negative patients. Here, CXCL13 is linked to central nervous system disorder.