Top

Fluids and Barriers of the CNS

Published in:

Open Access 01-12-2015 | Short paper

The chemokine CXCL13 is elevated in the cerebrospinal fluid of patients with neurosyphilis

Authors: R Dersch, T Hottenrott, M Senel, V Lehmensiek, H Tumani, S Rauer, O Stich

Published in: Fluids and Barriers of the CNS | Issue 1/2015

Abstract

Background

The chemokine CXCL13 has been discussed as a diagnostic parameter with high specificity for Lyme neuroborreliosis (LNB) and as a marker of disease activity. Neurosyphilis and LNB share similar characteristics. We investigated retrospectively CXCL13 levels in the cerebrospinal fluid (CSF) of patients with neurosyphilis at initial diagnosis and during treatment.

Results

Five patients with neurosyphilis were identified retrospectively using an electronic database in a tertiary care hospital from 2005 to 2012. CXCL13 levels were measured using an ELISA. Five patients with definite LNB and 10 patients with multiple sclerosis (MS) served as controls. Median CXCL13 levels at baseline were 972 pg/mL for neurosyphilis patients, 8,000 pg/mL for LNB patients, and 7.8 pg/mL for MS patients. Patients with LNB and neurosyphilis showed significantly higher CXCL13 levels in their CSF compared to MS patients (p < 0.05, p < 0.001, respectively). CXCL13 levels in the CSF declined during treatment.

Conclusion

CXCL13 levels in the CSF of patients with neurosyphilis can be as high as in patients with LNB, exceeding the proposed threshold of 250 pg/mL for the diagnosis of LNB. Patients with encephalitic/myelitic syndromes appear to have especially high levels of CXCL13. Clinicians should be aware that high levels of CXCL13 are not found exclusively in LNB but also in other infectious diseases of the CNS.

Centers for Disease Control and Prevention. Late and late latent syphilis—reported cases and rates of reported cases by state/area and region in alphabetical order, United States and outlying areas, 2009–2013. http://www.cdc.gov/std/stats13/tables/39.htm.

Robert Koch Institut. Syphilis in Deutschland 2012. Epidemiol Bull. 2013;44.

Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisakk P, Ransohoff RM, et al. Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain. 2006;129(Pt 1):200–11.PubMed

Senel M, Rupprecht TA, Tumani H, Pfister HW, Ludolph AC, Brettschneider J. The chemokine CXCL13 in acute neuroborreliosis. J Neurol Neurosurg Psychiatry. 2010;81(8):929–33.CrossRefPubMed

Hytonen J, Kortela E, Waris M, Puustinen J, Salo J, Oksi J. CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation. J Neuroinflammation. 2014;11:103.CrossRefPubMedCentralPubMed

Cerar T, Ogrinc K, Lotric-Furlan S, Kobal J, Levicnik-Stezinar S, Strle F, et al. Diagnostic value of cytokines and chemokines in Lyme neuroborreliosis. Clin Vaccine Immunol. 2013;20(10):1578–84.CrossRefPubMedCentralPubMed

Schmidt C, Plate A, Angele B, Pfister HW, Wick M, Koedel U, et al. A prospective study on the role of CXCL13 in Lyme neuroborreliosis. Neurology. 2011;76(12):1051–8.CrossRefPubMed

Tjernberg I, Henningsson AJ, Eliasson I, Forsberg P, Ernerudh J. Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the C6-peptide in Lyme neuroborreliosis. J Infect. 2011;62(2):149–58.CrossRefPubMed

van Burgel ND, Bakels F, Kroes AC, van Dam AP. Discriminating Lyme neuroborreliosis from other neuroinflammatory diseases by levels of CXCL13 in cerebrospinal fluid. J Clin Microbiol. 2011;49(5):2027–30.CrossRefPubMedCentralPubMed

10.

Albrecht P, Henke N, Lehmann HC, Macht S, Hefter H, Goebels N, et al. A case of relapsing-remitting neuroborreliosis? Challenges in the differential diagnosis of recurrent myelitis. Case Rep Neurol. 2012;4(1):47–53.CrossRefPubMedCentralPubMed

11.

Borde JP, Meier S, Fingerle V, Klier C, Hubner J, Kern WV. CXCL13 may improve diagnosis in early neuroborreliosis with atypical laboratory findings. BMC Infect Dis. 2012;12:344.CrossRefPubMedCentralPubMed

12.

Fischer L, Korfel A, Pfeiffer S, Kiewe P, Volk HD, Cakiroglu H, et al. CXCL13 and CXCL12 in central nervous system lymphoma patients. Clin Cancer Res. 2009;15(19):5968–73.CrossRefPubMed

13.

Rupprecht TA, Lechner C, Tumani H, Fingerle V. CXCL13: a biomarker for acute Lyme neuroborreliosis: investigation of the predictive value in the clinical routine. Nervenarzt. 2014;85:459–64.CrossRefPubMed

14.

Rupprecht TA, Kirschning CJ, Popp B, Kastenbauer S, Fingerle V, Pfister HW, et al. Borrelia garinii induces CXCL13 production in human monocytes through Toll-like receptor 2. Infect Immun. 2007;75(9):4351–6.CrossRefPubMedCentralPubMed

15.

Centers for Disease Control and Prevention. Update to CDC’s sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections. MMWR Morb Mortal Wkly Rep. 2012;61(31):590–4.

16.

DGN. S1 Leitlinie Neurosyphilis. In: Diener H-C, Weimar C, editors. Leitlinien für Diagnostik und Therapie in der Neurologie. Stuttgart: Thieme Verlag; 2012.

17.

Stanek G, Fingerle V, Hunfeld KP, Jaulhac B, Kaiser R, Krause A, et al. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect. 2011;17(1):69–79.CrossRefPubMed

18.

Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011;69(2):292–302.CrossRefPubMedCentralPubMed

19.

Schiffer L, Kielstein JT, Haubitz M, Luhrs H, Witte T, Haller H, et al. Elevation of serum CXCL13 in SLE as well as in sepsis. Lupus. 2011;20(5):507–11.CrossRefPubMed

20.

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.PubMedCentralPubMed

21.

Rupprecht TA, Plate A, Adam M, Wick M, Kastenbauer S, Schmidt C, et al. The chemokine CXCL13 is a key regulator of B cell recruitment to the cerebrospinal fluid in acute Lyme neuroborreliosis. J Neuroinflammation. 2009;6:42.CrossRefPubMedCentralPubMed

Title: The chemokine CXCL13 is elevated in the cerebrospinal fluid of patients with neurosyphilis
Authors: R Dersch
T Hottenrott
M Senel
V Lehmensiek
H Tumani
S Rauer
O Stich
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Fluids and Barriers of the CNS / Issue 1/2015
Electronic ISSN: 2045-8118
DOI: https://doi.org/10.1186/s12987-015-0008-8

At a glance: The STEP trials

Springer Medicine

The chemokine CXCL13 is elevated in the cerebrospinal fluid of patients with neurosyphilis

Abstract

Background

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2015

Nicotine pre-exposure reduces stroke-induced glucose transporter-1 activity at the blood–brain barrier in mice

Three-dimensional observation of Virchow–Robin spaces in the basal ganglia and white matter and their relevance to idiopathic normal pressure hydrocephalus

Vascular endothelial growth factor blockade alters magnetic resonance imaging biomarkers of vascular function and decreases barrier permeability in a rat model of lung cancer brain metastasis

The quest for a better insight into physiology of fluids and barriers of the brain: the exemplary career of Joseph D. Fenstermacher

The intrathecal, polyspecific antiviral immune response in neurosarcoidosis, acute disseminated encephalomyelitis and autoimmune encephalitis compared to multiple sclerosis in a tertiary hospital cohort

Adenosine receptor signaling: a key to opening the blood–brain door