eIn patients with syphilis, central nervous system (CNS) involvement is often difficult to determine. In patients who also are infected with human immunodeficiency virus (HIV), this is even more challenging, as cerebrospinal fluid (CSF) pleocytosis can be attributed to HIV, syphilis, or both. Hence, this study investigated (i) CSF chemokine (C-X-C motif) ligand 13 (CXCL13) as a potential marker to diagnose neurosyphilis in HIV-infected individuals and (ii) the added value of CSF CXCL13 to conventional CSF biomarkers, such as the rapid plasma reagin test (RPR), in diagnosing neurosyphilis. We included 103 syphilis patients from two centers in The Netherlands: 47 non-HIV-infected patients and 56 HIV-infected patients. A positive CSF-RPR was regarded as the gold standard for neurosyphilis. CSF CXCL13 levels were significantly higher in neurosyphilis patients when neurosyphilis was diagnosed by CSF-RPR (P ؍ 0.0002) than in the syphilis control group. The sensitivity and specificity of CSF CXCL13 (cutoff of 76.3 pg/ml) to diagnose neurosyphilis by using positive CSF-RPR as the gold standard were 50% and 90%, respectively. CSF CXCL13 had an added value to CSF-RPR positivity in 70% of HIV-positive patients and in 33% of HIV-negative patients. Our data show that CSF CXCL13 might be a potential additional marker in neurosyphilis when other markers are not conclusive. The added value of CSF CXCL13 measurement to the current neurosyphilis gold standard appears to benefit HIV-positive patients more than HIV-negative patients.
In 2007, the World Health Organization estimated an incidence of 12 million new infections with Treponema pallidum each year worldwide (1). Invasion of the central nervous system (CNS) by T. pallidum may occur during any disease stage of syphilis, leading to the development of neurosyphilis in some patients (2, 3). When dual infections with HIV and syphilis exist, the diagnostic challenge increases. A positive cerebrospinal fluid (CSF) Venereal Disease Research Laboratory test (VDRL) is generally considered the gold standard for neurosyphilis (4); however, several studies have clearly shown that a positive CSF rapid plasma reagin test (RPR) is an alternative to CSF-VDRL (5, 6), and RPR is also recommended by 2014 European guidelines (IUSTI-2014) (7). When the CSF-RPR or CSF-VDRL is negative, the diagnosis relies on other markers, like CSF pleocytosis, the CSF T. pallidum particle agglutination (TPPA) index, and clinical signs and symptoms.As the laboratory diagnosis of neurosyphilis is difficult, new markers are needed, and CSF B cell chemoattractant chemokine (C-X-C motif) ligand 13 (CXCL13) is currently forwarded as an interesting marker. CXCL13 has been demonstrated to be elevated in B lymphocyte-rich CSF (8, 9). CSF CXCL13 has a higher sensitivity than the established diagnostic markers for neuroborreliosis, such as CSF pleocytosis and Borrelia-specific antibodies (10). High numbers of B lymphocytes have also been observed in CSF from patients with syphilitic meningitis (11). CXCL13 dictates homi...