CXCL13 levels are more increased in cerebrospinal fluid and plasma of patients with acute infectious than in non-infectious diseases of the central nervous system

Brîndușa Țilea 1 , Septimiu Voidăzan 2 , Rodica Bălașa 3 , Adina Huțanu 4 ,  and Andrea Fodor 4
  • 1 Department M4 of Infectious Diseases, University of Medicine and Pharmacy Tîrgu Mureș, Romania
  • 2 Department of Epidemiology, University of Medicine and Pharmacy Tîrgu Mureș, Romania
  • 3 Department M4 Division of Neurology, University of Medicine and Pharmacy Tîrgu Mureș, Romania
  • 4 Department M2 Laboratory Medicine, Emergency Clinical County Hospital Tîrgu Mureș, Romania


Background: During the acute inflammatory process, the CXCL13 chemokine plays an important role in B cell recruitment within the central nervous system (CNS).

Objective: The objective of the study consisted of the evaluation of CXCL13 chemokine cerebral spinal fluid (CSF) and plasma levels in patients with acute infectious and non-infectious neurological diseases correlated with pleocytosis and CSF protein levels.

Material and method: This retrospective study was conducted over one year and included 72 patients. Thirty-eight patients (52.8%) suffering from infectious neurological disease, acute viral and bacterial meningitis, meningoencephalitis, and 34 patients (44.2%) diagnosed with non-infectious neurological diseases.

CXCL13 chemokine CSF and plasma levels were determined through the ELISA technique with the Human CXCL13/BLC/BCA-1 kit. CSF cell count, glucose and protein levels, along with anti-Borrelia burgdorferi antibodies were monitored using the ELISA technique.

Results: CXCL13 chemokine levels in the CSF of patients with acute infectious neurological diseases showed a median value of 23.07 pg/mL, which was significantly higher in comparison with the median value of 11.5 pg/mL of patients with noninfectious neurological diseases (p-0.03). CXCL13 median plasma concentration in patients with infectious neurological diseases was 108.1 pg/mL, in comparison with the second patient category, 50.7 pg/ml (p-0.001). We observed a statistically significant association between CXCL13 concentrations, CSF cell count and proteins. The higher the CXCL13 chemokine level, the more increased the cell count was.

Conclusions: CXCL13 levels in the CSF was significantly increased in patients with acute infectious neurological diseases compared with patients with non-infectious diseases. Moreover, CXCL13 chemokine concentration was significantly correlated with the number of cells and proteins in the CSF of patients suffering from neuroinfections.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Magliozzi R, Columba Cabezas S, Serafini B, Aloisi F. Intracerebral expression of CXCL13 and BAFF is accompanied by formation of lymphoid follicle-like structures in the meninges of mice with relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol. 2004 Mar;148(1-2):11-23. DOI: 10.1016/j.jneuroim.2003.10.056.

  • 2. Kowarik MC, Cepoc S, Sellner J, Grumel V, Weber M, Korn T, et al. CXCL13 is a major determinant for B cell recruitment to the CSF during neuroinflammation. J of Neuroinflamm. 2012 May;9:93. DOI: 10.1186/1742-2094-9-93.

  • 3. Hytonen J, Kortela E, Waris M, Puustinen J, Oksi J. CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation. J of Neuroinflamm. 2014 Jun;11:103. DOI: 10.1186/1742-2094-11-103.

  • 4. Bremell D, Mattsson N, Edsbagge M, Blennow K, Andreasson U, Wikkelso C, et al. Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection. BMC Neurol. 2013 Jan;13:2. DOI: 10.1186/1471-2377-13-2.

  • 5. Fujimori J, Nakashima I, Kuroda H, Fujihara K, Aoki M. Cerebrospinal fluid CXCL13 a prognostic marker for aseptic meningitis. J Neuroimmunol. 2014 Aug; 273(1-2):77-84. DOI: 10.1016/j.jneuroim.2014.05.008.

  • 6. 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 Jan; 129(Pt1):200-11.

  • 7. Schmidt C, Plate A, Angele B, Pfister H-W, Wick M, Koede U, et al. A prospective study on the role of CXCL13 in Lyme neuroborreliosis. Neurology. 2011 Mar;76 (12):1051-8. DOI: 10.1212/WNL.0b013e318211c39a.

  • 8. van Burgel ND, Bakels F, Kroes ACM, van Dam AP. Discriminating Lyme Neuroborreliosis from other Neuroinflammatory diseases by levels of CXCL13 in cerebrospinal fluid. J Clin Microbial. 2011 May;49(5):2027-30. DOI: 10.1128/JCM.00084-11.

  • 9. Stanek G, Wormser GP, Gray J, Srtle F. Lyme borreliosis. Lancet. 2012 Feb; 379(9814):461-73. DOI: 10.1016/S0140-6736(11)60103-7.

  • 10. Mygland A, Ljøstad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I, et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010 Jan;17(1):8-16. DOI: 10.1111/j.1468-1331.2009.02862.x.

  • 11. Lalor SJ, Segal BM. Lymphoid chemokines in the CNS. J Neuroimmunol. 2010 Jul;224(1-2):56-61. DOI: 10.1016/j.jneuroim.2010.05.017.

  • 12. Wutte N, Berghold A, Löffler S, Zenz W, Daghofer E, Krainberger I, et al. CXCL13 chemokine in paediatric and adult neuroborreliosis. Acta Neurol Scand. 2011 Nov;124(5):321-8. DOI: 10.1111/j.1600-0404.2010.01477.x.

  • 13. Ljøstad U, Mygland A. CSF B-lymphocyte chemoattractant (CXCL13) in the early diagnosis of Lyme neuroborreliosis. J Neurol. 2008 May;255(5):732-7. DOI: 10.1007/s00415-008-0785-y DOI: 10.1007/s00415-008-0974-8.

  • 14. Hagberg L, Cinque P, Gisslen M, Brew BJ, Spudich S, Bestetti A, et al. Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection. AIDS Res Ther. 2010 Jun;7:15. DOI: 10.1186/1742-6405-7-15.

  • 15. Tiberti N, Hainard A, Lejon V, Courtioux B, Matovu E, Enyaru JC, et al. Cerebrospinal fluid neopterin as marker of the meningo-encephalitic stage of Trypanosoma brucei gambiense sleeping sickness. PLoS One. 2012 Jul;7(7): e40909. DOI: 10.1371/journal.pone.0040909.

  • 16. Borde JP, Meier S, Fingerle V, Klier C, Hübner J, Kern WV. CXCL13 may improve diagnosis in early neuroborreliosis with atypical laboratory findings. BMC Infect Dis. 2012 Dec;12:344. DOI: 10.1186/1471-2334-12-344.

  • 17. Tumani H, Cadavid D. Are high CSF levels of CXCL13 helpful for diagnosis of Lyme neuroborreliosis? Neurology. 2011 Mar;76(12):1034-5. DOI: 10.1212/WNL.0b013e318211c3ed.

  • 18. Ciurtioux B, Pervieux L, Vatunga G, Marin B, Josenando T, Jauberteau-Marchan, et al. Increased CXCL-13 levels in human African trypanosomiasis meningoencephalitis. Trop Med Int Health. 2009 May;14(5):529-534. DOI: 10.1111/j.1365-3156.2009.02263.x.

  • 19. Rupprecht TA, Pfister HW, Angele B, Kastenbauer S, Wilske B, Koedel U. The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis. Neurol. 2005 Aug;65(3):448-50. DOI: 10.1212/01.wnl.0000171349.06645.79.

  • 20. 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. DOI: 10.1136/jnnp.2009.195438.

  • 21. Widney DP, Breen EC, Boscardin WJ, Kitchen SG, Alcantar JM, Smith JB, et al. Serum levels of the homeostatic B cell chemokine, CXCL13, are elevated during HIV infection. J Interferon Cytokine Res. 2005 Nov;25(11):702-6. DOI: 10.1089/jir.2005.25.702.

  • 22. Cagigi A, Mowafi F, Phuong Dang LV, Tenner-Racz K, Atlas A, Grutzmeier S, et al. Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B cells during chronic HIV-1 infection. Blood. 2008 Dec;112(12):4401-10. DOI: 10.1182/blood-2008-02-140426.

  • 23. Rupprecht TA, Koedel U, Angele B, Fingerle V, Pfister HW. Cytokine CXCL13: a possible early CSF marker for neuroborreliosis. Nervenarzt. 2006 Apr; 77(4):470-473. DOI: 10.1007/s00115-005-2021-7.

  • 24. Tjernberg L, Henningsson AJ, Eliasson I, Forsberg P, Ernerudh J. Diagnostic performance of cerebrospinal fluid chemokine CXCL13 and antibodies to the Co-peptide in Lyme neuroborreliosis. J Infect. 2010 Feb;62(2):149-58. DOI: 10.1016/j.jinf.2010.11.005.

  • 25. Sellebjerg F, Bornsen L, Khademi M, Krakaver M. Increased cerebrospinal fluid concentrations of the chemokine CXCL13 in active MS. Neurology. 2009 Dec;73(23):2003-10. DOI: 10.1212/WNL.0b013e3181c5b457.

  • 26. Schiffer L, Kumpers P, Devalos AM, Haubitz M, Haller H, Anders HJ, et al. B-cell attracting chemokine CXCL13 as a marker of disease activity and renal involvement in systemic lupus erythematosus. Nephrol Dial Transplant. 2009 Dec; 24(12):3780-12. DOI: 10.1093/ndt/gfp343.


Journal + Issues