Use of cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis: a three-case report




CXCL13, Neurosyphilis, cerebrospinal fluid, TReponema pallidum


Introduction: Previous retrospective studies have demonstrated that the concentration of chemokine ligand CXCL13 in cerebrospinal fluid (CSF-CXCL13) is a promising biomarker in the diagnosis of neurosyphilis and, additionally, in the monitoring of therapeutic efficacy. Objective: To describe three cases of patients with neurosyphilis (NS) treated at Hospital Universitário Gaffrée e Guinle, in Rio de Janeiro, Brazil, with suspected active syphilis with neurological symptoms. Case report: Three patients from Rio de Janeiro, Brazil, were investigated for symptomatic NS. The concentration of CSF-CXCL13 was prospectively performed by enzyme-linked immunosorbent assay (ELISA) in all participants at baseline and in follow-up visits at 3 months after therapy. CSF-CXCL13 concentrations were significantly higher in all three patients with established NS. The CSF-CXCL13 concentrations decreased after 3 months of therapy compared to baseline in all cases reported. The added high concentration of CSF-CXCL13 plus CSF-TPHA reactivity above 1:40 titer agreed with the diagnosis of NS in 100% of the cases. Conclusion: In this case series, we present three cases of NS diagnosed using CXCL13 in CSF as a complementary test. These case series suggest that the clinical use of CSF-CXCL13 is useful as a supplementary biomarker for NS and for monitoring the effectiveness of NS therapy, especially in patients with nonreactive CSF-VDRL, excluding other neurologic diseases.


Download data is not yet available.


Collart P, Franceschini P, Durel P. Experimental rabbit syphilis. Br J Vener Dis. 1971;47(6):389-400.

Ghanem KG. REVIEW: neurosyphilis: a historical perspective and review. CNS Neurosci Ther. 2010;16(5):e157-e68.

Domingues CSB, Lannoy LH, Saraceni V, Cunha ARC, Pereira GFM. Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: vigilância epidemiológica. Epidemiol Serv Saúde. 2021;30(1):e2020549.

Eckman EA, Clausen DM, Herdt AR, Pacheco-Quinto J, Halperin JJ. Specificity and diagnostic utility of cerebrospinal fluid CXCL13 in lyme neuroborreliosis. Clin Infect Dis. 2021;72(10):1719-26.

Marra CM, Tantalo LC, Sahi SK, Maxwell CL, Lukehart SA. CXCL13 as a cerebrospinal fluid marker for neurosyphilis in HIV-infected patients with syphilis. Sex Transm Dis. 2010;37(5):283-7.

Dersch R, Hottenrott T, Senel M, Lehmensiek V, Tumani H, Rauer S, et al. The chemokine CXCL13 is elevated in the cerebrospinal fluid of patients with neurosyphilis. Fluids Barriers CNS. 2015;12:12.

Mothapo KM, Verbeek MM, van der Velden LB, Ang CW, Koopmans PP, van der Ven A, et al. Has CXCL13 an added value in diagnosis of neurosyphilis? J Clin Microbiol. 2015;53(5):1693-6.

Hu R, Lu C, Lu S, Hu Y, Ma H, Lai W, et al. Value of CXCL13 in diagnosing asymptomatic neurosyphilis in HIV-infected patients. Int J STD AIDS. 2016;27(2):141-6.

Zeng YL, Lin YQ, Zhang NN, Zou CN, Zhang HL, Peng F, et al. CXCL13 chemokine as a promising biomarker to diagnose neurosyphilis in HIV-negative patients. Springerplus. 2016;5(1):743.

Gudowska-Sawczuk M, Mroczko B. Chemokine ligand 13 (CXCL13) in neuroborreliosis and neurosyphilis as selected spirochetal neurological diseases: a review of its diagnostic significance. Int J Mol Sci. 2020;21(8):2927.

Gonzalez H, Koralnik IJ, Marra CM. Neurosyphilis. Semin Neurol. 2019;39(4):448-55.

Marra CM. Neurosyphilis. Continuum (Minneap Minn). 2015;21(6 Neuroinfectious Disease):1714-28.

Berger JR, Dean D. Neurosyphilis. Handb Clin Neurol. 2014;121:1461-72.

Bhai S, Lyons JL. Neurosyphilis update: atypical is the new typical. Curr Infect Dis Rep. 2015;17(5):481.

Centurion-Lara A, Molini BJ, Godornes C, Sun E, Hevner K, Van Voorhis WC, et al. Molecular differentiation of Treponema pallidum subspecies. J Clin Microbiol. 2006;44(9):3377-80.

Marra CM, Maxwell CL, Dunaway SB, Sahi SK, Tantalo LC. Cerebrospinal fluid treponema pallidum particle agglutination assay for neurosyphilis diagnosis. J Clin Microbiol. 2017;55(6):1865-70.

Marra CM. Alternatives to the cerebrospinal fluid venereal disease research laboratory test for neurosyphilis diagnosis. Sex Transm Dis. 2021;48(8S):S54-S57.

Yu Q, Cheng Y, Wang Y, Wang C, Lu H, Guan Z, et al. Aberrant humoral immune responses in neurosyphilis: CXCL13/CXCR5 play a pivotal role for b-cell recruitment to the cerebrospinal fluid. J Infect Dis. 2017;216(5):534-44.

Kojima Y, Furubayashi K, Kawahata T, Mori H, Komano J. Circulation of distinct treponema pallidum strains in individuals with heterosexual orientation and men who have sex with men. J clin Microbiol. 2019;57(1):e01148-18.




How to Cite

Carvalho R de S, Rangel I de C, Soane MM, Lopes MQP, Ferry FR de A. Use of cerebrospinal fluid CXCL13 concentration for diagnosis and monitoring of neurosyphilis: a three-case report. DST [Internet]. 2023 Nov. 27 [cited 2024 Apr. 14];35. Available from:



Case Report