CXCL13 in Cerebrospinal Fluid: Clinical Value in a Large Cross-Sectional Study

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jan 11

PMID 38203597

Authors

Deborah Katharina Erhart

Veronika Klose

Tatjana Schaper

Hayrettin Tumani

Makbule Senel

Affiliations

Soon will be listed here.

Abstract

C-X-C-motif chemokine ligand 13 (CXCL13) in cerebrospinal fluid (CSF) is increasingly used in clinical routines, although its diagnostic specificity and divergent cut-off values have been defined so far mainly for neuroborreliosis. Our aim was to evaluate the value of CSF-CXCL13 as a diagnostic and treatment response marker and its role as an activity marker in a larger disease spectrum, including neuroborreliosis and other neuroinflammatory and malignant CNS-disorders. Patients who received a diagnostic lumbar puncture (LP) ( = 1234) between July 2009 and January 2023 were included in our retrospective cross-sectional study. The diagnostic performance of CSF-CXCL13 for acute neuroborreliosis was highest at a cut-off of 428.92 pg/mL (sensitivity: 92.1%; specificity: 96.5%). In addition, CXCL13 levels in CSF were significantly elevated in multiple sclerosis with clinical ( = 0.001) and radiographic disease activity ( < 0.001). The clinical utility of CSF-CXCL13 appears to be multifaceted. CSF-CXCL13 is significantly elevated in patients with neuroborreliosis and shows a rapid and sharp decline with antibiotic therapy, but it is not specific for this disease and is also highly elevated in less common subacute neuroinfectious diseases, such as neurosyphilis and cryptococcal meningitis or in primary/secondary B-cell lymphoma.

Citing Articles

Integrated multi-biomarker panel of CXCL13, HS-CRP, and WBC counts predicts outcomes in stroke neurosyphilis patients treated with HBO and TUS-NMES.

He W, Chen S, Chen R, Zhang J, Zhang X, Wu M Front Neurol. 2025; 16:1530447.

PMID: 40070668 PMC: 11894733. DOI: 10.3389/fneur.2025.1530447.

Borrelia spielmanii-Associated Neuroborreliosis in Patient Receiving Rituximab, Belgium.

Carette T, Lebrun L, Kabamba-Mukadi B, Raymackers J, Bayart J Emerg Infect Dis. 2025; 31(2):341-344.

PMID: 39983686 PMC: 11845155. DOI: 10.3201/eid3102.240777.

CXCL13 as a Biomarker: Background and Utility in Multiple Sclerosis.

Pachner A, Pike S, Smith A, Gilli F Biomolecules. 2025; 14(12.

PMID: 39766248 PMC: 11673926. DOI: 10.3390/biom14121541.

Cerebrospinal Fluid Cytology in Lyme Neuroborreliosis Revisited-Role of Neutrophilic Granulocytes: A Retrospective Single-Center Study.

Otto F, Wipfler P, Hitzl W, Preisel M, Harrer A, Pilz G J Clin Med. 2024; 13(23).

PMID: 39685862 PMC: 11641970. DOI: 10.3390/jcm13237406.

CXCL13: a common target for immune-mediated inflammatory diseases.

Hui L, Li Y, Huang M, Jiang Y, Liu T Clin Exp Med. 2024; 24(1):244.

PMID: 39443356 PMC: 11499446. DOI: 10.1007/s10238-024-01508-8.

References

Stanek G, Fingerle V, Hunfeld K, Jaulhac B, Kaiser R, Krause A . Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect. 2010; 17(1):69-79. DOI: 10.1111/j.1469-0691.2010.03175.x. View

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

. Evaluation of diagnostic ('classification') criteria in Behçet's disease--towards internationally agreed criteria. The International Study Group for Behçet's disease. Br J Rheumatol. 1992; 31(5):299-308. View

Eckman E, Clausen D, Herdt A, Pacheco-Quinto J, Halperin J . Specificity and Diagnostic Utility of Cerebrospinal Fluid CXCL13 in Lyme Neuroborreliosis. Clin Infect Dis. 2020; 72(10):1719-1726. DOI: 10.1093/cid/ciaa335. View

Maeyama M, Sasayama T, Tanaka K, Nakamizo S, Tanaka H, Nishihara M . Multi-marker algorithms based on CXCL13, IL-10, sIL-2 receptor, and β2-microglobulin in cerebrospinal fluid to diagnose CNS lymphoma. Cancer Med. 2020; 9(12):4114-4125. PMC: 7300423. DOI: 10.1002/cam4.3048. View

Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisakk P, Ransohoff R . Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain. 2005; 129(Pt 1):200-11. DOI: 10.1093/brain/awh680. View

Masouris I, Manz K, Pfirrmann M, Dreyling M, Angele B, Straube A . CXCL13 and CXCL9 CSF Levels in Central Nervous System Lymphoma-Diagnostic, Therapeutic, and Prognostic Relevance. Front Neurol. 2021; 12:654543. PMC: 8032970. DOI: 10.3389/fneur.2021.654543. View

DiSano K, Gilli F, Pachner A . Intrathecally produced CXCL13: A predictive biomarker in multiple sclerosis. Mult Scler J Exp Transl Clin. 2021; 6(4):2055217320981396. PMC: 7747124. DOI: 10.1177/2055217320981396. View

Knudtzen F, Nilsson A, Hovius J, Skarphedinsson S . The predictive value of CXCL13 in suspected Lyme neuroborreliosis: a retrospective cross-sectional study. Eur J Clin Microbiol Infect Dis. 2020; 39(8):1461-1470. DOI: 10.1007/s10096-020-03861-4. View

10.

Novakova L, Axelsson M, Khademi M, Zetterberg H, Blennow K, Malmestrom C . Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis. J Neurochem. 2016; 141(2):296-304. DOI: 10.1111/jnc.13881. View

11.

Zhong X, Wang H, Dai Y, Wu A, Bao J, Xu W . Cerebrospinal fluid levels of CXCL13 are elevated in neuromyelitis optica. J Neuroimmunol. 2011; 240-241:104-8. DOI: 10.1016/j.jneuroim.2011.10.001. View

12.

Erhart D, Bracknies V, Lutz-Schuhbauer S, Wigand S, Tumani H . The special role of CXCL13 in Lyme neuroborreliosis: a case report. Neurol Res Pract. 2022; 4(1):3. PMC: 8762870. DOI: 10.1186/s42466-022-00167-y. View

13.

Teunissen C, Tumani H, Engelborghs S, Mollenhauer B . Biobanking of CSF: international standardization to optimize biomarker development. Clin Biochem. 2014; 47(4-5):288-92. DOI: 10.1016/j.clinbiochem.2013.12.024. View

14.

Rupprecht T, Manz K, Fingerle V, Lechner C, Klein M, Pfirrmann M . Diagnostic value of cerebrospinal fluid CXCL13 for acute Lyme neuroborreliosis. A systematic review and meta-analysis. Clin Microbiol Infect. 2018; 24(12):1234-1240. DOI: 10.1016/j.cmi.2018.04.007. View

15.

Helliwell A, Stockwell P, Edgar C, Chatterjee A, Tate W . Dynamic Epigenetic Changes during a Relapse and Recovery Cycle in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Int J Mol Sci. 2022; 23(19). PMC: 9570248. DOI: 10.3390/ijms231911852. View

16.

Reiber H . Flow rate of cerebrospinal fluid (CSF)--a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci. 1994; 122(2):189-203. DOI: 10.1016/0022-510x(94)90298-4. View

17.

Picha D, Moravcova L, Smiskova D . Prospective study on the chemokine CXCL13 in neuroborreliosis and other aseptic neuroinfections. J Neurol Sci. 2016; 368:214-20. DOI: 10.1016/j.jns.2016.05.059. View

18.

Lintner H, Hochgatterer-Rechberger P, Pischinger B, Seier J, Vollmann P, Haushofer A . Sensitivity and specificity of cerebrospinal fluid CXCL13 for diagnosing Lyme neuroborreliosis - a study on 1410 patients and review of the literature. J Neurol Sci. 2020; 414:116843. DOI: 10.1016/j.jns.2020.116843. View

19.

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. PMC: 4070086. DOI: 10.1186/1742-2094-11-103. View

20.

Zajkowska J, Moniuszko-Malinowska A, Pancewicz S, Muszynska-Mazur A, Kondrusik M, Grygorczuk S . Evaluation of CXCL10, CXCL11, CXCL12 and CXCL13 chemokines in serum and cerebrospinal fluid in patients with tick borne encephalitis (TBE). Adv Med Sci. 2011; 56(2):311-7. DOI: 10.2478/v10039-011-0033-z. View