Skip to main content
Erschienen in: Journal of Neurology 1/2018

13.11.2017 | Original Communication

CXCL13 as a diagnostic marker of neuroborreliosis and other neuroinflammatory disorders in an unselected group of patients

verfasst von: Judith N. Wagner, S. Weis, C. Kubasta, J. Panholzer, T. J. von Oertzen

Erschienen in: Journal of Neurology | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Abstract

Background

The C-X-C motif chemokine ligand 13 (CXCL13) and its receptor CXCR5 play an important role in the homing of B-lymphocytes. As a biomarker in the cerebrospinal fluid (CSF), CXCL13 has increasingly been used for the diagnosis of neuroborreliosis (NB). We evaluated the diagnostic and prognostic potential of CXCL13 for NB and other neuroinflammatory diseases in an unselected cohort, paying attention to those patients particularly who might benefit from newly emerging CXCL13-directed therapies.

Methods

We report the CSF CXCL13 concentrations and other relevant baseline characteristics for an unselected cohort of 459 patients. We compare different diagnostic groups and analyse the sensitivity and specificity of CSF CXCL13 as a marker of NB. The course of the CXCL13 concentrations is reported in a subgroup of 19 patients.

Results

We confirm the high diagnostic yield of CXCL13 for NB in this unselected cohort. The optimal cut-off for the reliable diagnosis of NB was 93.83 pg/ml, resulting in a sensitivity and specificity of 95 and 97%, respectively (positive predictive value 55.9%, negative predictive value 99.8%), surpassing the sensitivity of both serological testing and PCR. CSF CXCL13 concentration showed a swift response to therapy. Non-NB patients with high CSF CXCL13 concentrations suffered from meningeosis neoplastica or infectious encephalitis.

Conclusions

CXCL13 is a valuable tool for the diagnosis and assessment of therapeutic response in NB. Furthermore, our data point towards an emerging role of CXCL13 in the diagnosis and prognosis of viral encephalitis and meningeosis neoplastica. These results are of particular interest in the light of recently developed approaches to CXCL13-directed therapeutic interventions.
Literatur
1.
Zurück zum Zitat van Burgel ND, Bakels F, Kroes ACM, van Dam AP (2011) Discriminating Lyme neuroborreliosis from other neuroinflammatory diseases by levels of CXCL13 in cerebrospinal fluid. J Clin Microbiol 49:2027–2030CrossRefPubMedPubMedCentral van Burgel ND, Bakels F, Kroes ACM, van Dam AP (2011) Discriminating Lyme neuroborreliosis from other neuroinflammatory diseases by levels of CXCL13 in cerebrospinal fluid. J Clin Microbiol 49:2027–2030CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Klimatcheva E, Pandina T, Reilly C, Torno S, Bussler H, Scrivens M et al (2015) CXCL13 antibody for the treatment of autoimmune disorders. BMC Immunol 16:6CrossRefPubMedPubMedCentral Klimatcheva E, Pandina T, Reilly C, Torno S, Bussler H, Scrivens M et al (2015) CXCL13 antibody for the treatment of autoimmune disorders. BMC Immunol 16:6CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Widney DP, Breen EC, Boscardin WJ, Kitchen SG, Alcantar JM, Smith JB et al (2005) Serum levels of the homeostatic B cell chemokine, CXCL13, are elevated during HIV infection. J Interferon Cytokine Res Off J Int Soc Interferon Cytokine Res 25:702–706CrossRef Widney DP, Breen EC, Boscardin WJ, Kitchen SG, Alcantar JM, Smith JB et al (2005) Serum levels of the homeostatic B cell chemokine, CXCL13, are elevated during HIV infection. J Interferon Cytokine Res Off J Int Soc Interferon Cytokine Res 25:702–706CrossRef
4.
Zurück zum Zitat Senel M, Rupprecht TA, Tumani H, Pfister HW, Ludolph AC, Brettschneider J (2010) The chemokine CXCL13 in acute neuroborreliosis. J Neurol Neurosurg Psychiatry 81:929–933CrossRefPubMed Senel M, Rupprecht TA, Tumani H, Pfister HW, Ludolph AC, Brettschneider J (2010) The chemokine CXCL13 in acute neuroborreliosis. J Neurol Neurosurg Psychiatry 81:929–933CrossRefPubMed
5.
Zurück zum Zitat Schmidt C, Plate A, Angele B, Pfister H-W, Wick M, Koedel U et al (2011) A prospective study on the role of CXCL13 in Lyme neuroborreliosis. Neurology 76:1051–1058CrossRefPubMed Schmidt C, Plate A, Angele B, Pfister H-W, Wick M, Koedel U et al (2011) A prospective study on the role of CXCL13 in Lyme neuroborreliosis. Neurology 76:1051–1058CrossRefPubMed
6.
Zurück zum Zitat Kothur K, Wienholt L, Brilot F, Dale RC (2016) CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: a systematic review. Cytokine 77:227–237CrossRefPubMed Kothur K, Wienholt L, Brilot F, Dale RC (2016) CSF cytokines/chemokines as biomarkers in neuroinflammatory CNS disorders: a systematic review. Cytokine 77:227–237CrossRefPubMed
7.
Zurück zum Zitat Alvarez E, Piccio L, Mikesell RJ, Klawiter EC, Parks BJ, Naismith RT et al (2013) CXCL13 is a biomarker of inflammation in multiple sclerosis, neuromyelitis optica, and other neurological conditions. Mult Scler Houndmills Basingstoke Engl 19:1204–1208CrossRef Alvarez E, Piccio L, Mikesell RJ, Klawiter EC, Parks BJ, Naismith RT et al (2013) CXCL13 is a biomarker of inflammation in multiple sclerosis, neuromyelitis optica, and other neurological conditions. Mult Scler Houndmills Basingstoke Engl 19:1204–1208CrossRef
10.
Zurück zum Zitat Kaplan RF, Trevino RP, Johnson GM, Levy L, Dornbush R, Hu LT et al (2003) Cognitive function in post-treatment Lyme disease: do additional antibiotics help? Neurology 60:1916–1922CrossRefPubMed Kaplan RF, Trevino RP, Johnson GM, Levy L, Dornbush R, Hu LT et al (2003) Cognitive function in post-treatment Lyme disease: do additional antibiotics help? Neurology 60:1916–1922CrossRefPubMed
11.
Zurück zum Zitat Bremell D, Mattsson N, Edsbagge M, Blennow K, Andreasson U, Wikkelsö C et al (2013) Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection. BMC Neurol 13:2CrossRefPubMedPubMedCentral Bremell D, Mattsson N, Edsbagge M, Blennow K, Andreasson U, Wikkelsö C et al (2013) Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection. BMC Neurol 13:2CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Henningsson AJ, Gyllemark P, Lager M, Skogman BH, Tjernberg I (2016) Evaluation of two assays for CXCL13 analysis in cerebrospinal fluid for laboratory diagnosis of Lyme neuroborreliosis. APMIS Acta Pathol Microbiol Immunol Scand 124:985–990CrossRef Henningsson AJ, Gyllemark P, Lager M, Skogman BH, Tjernberg I (2016) Evaluation of two assays for CXCL13 analysis in cerebrospinal fluid for laboratory diagnosis of Lyme neuroborreliosis. APMIS Acta Pathol Microbiol Immunol Scand 124:985–990CrossRef
13.
Zurück zum Zitat Henningsson AJ, Christiansson M, Tjernberg I, Löfgren S, Matussek A (2014) Laboratory diagnosis of Lyme neuroborreliosis: a comparison of three CSF anti-Borrelia antibody assays. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol 33:797–803CrossRef Henningsson AJ, Christiansson M, Tjernberg I, Löfgren S, Matussek A (2014) Laboratory diagnosis of Lyme neuroborreliosis: a comparison of three CSF anti-Borrelia antibody assays. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol 33:797–803CrossRef
14.
Zurück zum Zitat Kowarik MC, Cepok S, Sellner J, Grummel V, Weber MS, Korn T et al (2012) CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation 9:93CrossRefPubMedPubMedCentral Kowarik MC, Cepok S, Sellner J, Grummel V, Weber MS, Korn T et al (2012) CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation. J Neuroinflammation 9:93CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Lee EJ, Kim YH, Lee JY, Sunwoo J-S, Park SY, Kim TH (2017) Acute HIV-1 infection presenting with fulminant encephalopathy. Int J STD AIDS 28:1041–1044CrossRefPubMed Lee EJ, Kim YH, Lee JY, Sunwoo J-S, Park SY, Kim TH (2017) Acute HIV-1 infection presenting with fulminant encephalopathy. Int J STD AIDS 28:1041–1044CrossRefPubMed
16.
Zurück zum Zitat Helleberg M, Kirk O (2013) Encephalitis in primary HIV infection: challenges in diagnosis and treatment. Int J STD AIDS 24:489–493CrossRefPubMed Helleberg M, Kirk O (2013) Encephalitis in primary HIV infection: challenges in diagnosis and treatment. Int J STD AIDS 24:489–493CrossRefPubMed
17.
Zurück zum Zitat Ferrada MA, Xie Y, Nuermberger E (2015) Primary HIV infection presenting as limbic encephalitis and rhabdomyolysis. Int J STD AIDS 26:835–836CrossRefPubMed Ferrada MA, Xie Y, Nuermberger E (2015) Primary HIV infection presenting as limbic encephalitis and rhabdomyolysis. Int J STD AIDS 26:835–836CrossRefPubMed
18.
Zurück zum Zitat Vinuesa CG, Sanz I, Cook MC (2009) Dysregulation of germinal centres in autoimmune disease. Nat Rev Immunol 9:845–857CrossRefPubMed Vinuesa CG, Sanz I, Cook MC (2009) Dysregulation of germinal centres in autoimmune disease. Nat Rev Immunol 9:845–857CrossRefPubMed
19.
Zurück zum Zitat Festa ED, Hankiewicz K, Kim S, Skurnick J, Wolansky LJ, Cook SD et al (2009) Serum levels of CXCL13 are elevated in active multiple sclerosis. Mult Scler Houndmills Basingstoke Engl 15:1271–1279CrossRef Festa ED, Hankiewicz K, Kim S, Skurnick J, Wolansky LJ, Cook SD et al (2009) Serum levels of CXCL13 are elevated in active multiple sclerosis. Mult Scler Houndmills Basingstoke Engl 15:1271–1279CrossRef
20.
Zurück zum Zitat Bürkle A, Niedermeier M, Schmitt-Gräff A, Wierda WG, Keating MJ, Burger JA (2007) Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B-cell chronic lymphocytic leukemia. Blood 110:3316–3325CrossRefPubMed Bürkle A, Niedermeier M, Schmitt-Gräff A, Wierda WG, Keating MJ, Burger JA (2007) Overexpression of the CXCR5 chemokine receptor, and its ligand, CXCL13 in B-cell chronic lymphocytic leukemia. Blood 110:3316–3325CrossRefPubMed
21.
Zurück zum Zitat Fischer L, Korfel A, Pfeiffer S, Kiewe P, Volk H-D, Cakiroglu H et al (2009) CXCL13 and CXCL12 in central nervous system lymphoma patients. Clin Cancer Res Off J Am Assoc Cancer 15:5968–5973CrossRef Fischer L, Korfel A, Pfeiffer S, Kiewe P, Volk H-D, Cakiroglu H et al (2009) CXCL13 and CXCL12 in central nervous system lymphoma patients. Clin Cancer Res Off J Am Assoc Cancer 15:5968–5973CrossRef
22.
Zurück zum Zitat Rubenstein JL, Wong VS, Kadoch C, Gao H-X, Barajas R, Chen L et al (2013) CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood 121:4740–4748CrossRefPubMedPubMedCentral Rubenstein JL, Wong VS, Kadoch C, Gao H-X, Barajas R, Chen L et al (2013) CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood 121:4740–4748CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Biswas S, Sengupta S, Roy Chowdhury S, Jana S, Mandal G, Mandal PK et al (2014) CXCL13-CXCR5 co-expression regulates epithelial to mesenchymal transition of breast cancer cells during lymph node metastasis. Breast Cancer Res Treat 143:265–276CrossRefPubMed Biswas S, Sengupta S, Roy Chowdhury S, Jana S, Mandal G, Mandal PK et al (2014) CXCL13-CXCR5 co-expression regulates epithelial to mesenchymal transition of breast cancer cells during lymph node metastasis. Breast Cancer Res Treat 143:265–276CrossRefPubMed
24.
Zurück zum Zitat Singh R, Gupta P, Kloecker GH, Singh S, Lillard JW (2014) Expression and clinical significance of CXCR5/CXCL13 in human non-small cell lung carcinoma. Int J Oncol 45:2232–2240CrossRefPubMedPubMedCentral Singh R, Gupta P, Kloecker GH, Singh S, Lillard JW (2014) Expression and clinical significance of CXCR5/CXCL13 in human non-small cell lung carcinoma. Int J Oncol 45:2232–2240CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Zhu Z, Zhang X, Guo H, Fu L, Pan G, Sun Y (2015) CXCL13-CXCR5 axis promotes the growth and invasion of colon cancer cells via PI3K/AKT pathway. Mol Cell Biochem 400:287–295CrossRefPubMed Zhu Z, Zhang X, Guo H, Fu L, Pan G, Sun Y (2015) CXCL13-CXCR5 axis promotes the growth and invasion of colon cancer cells via PI3K/AKT pathway. Mol Cell Biochem 400:287–295CrossRefPubMed
Metadaten
Titel
CXCL13 as a diagnostic marker of neuroborreliosis and other neuroinflammatory disorders in an unselected group of patients
verfasst von
Judith N. Wagner
S. Weis
C. Kubasta
J. Panholzer
T. J. von Oertzen
Publikationsdatum
13.11.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 1/2018
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-017-8669-7

Weitere Artikel der Ausgabe 1/2018

Journal of Neurology 1/2018 Zur Ausgabe

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.