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CXCL13 in laboratory diagnosis of Lyme neuroborreliosis

The B cell-attracting chemokine CXCL13 has shown to be a useful and reliable test in addition to serology for the diagnosis of the acute Lyme neuroborreliosis.

CXCL13 is a B-cell-attracting chemokine. Initially, the role of this chemokine was assumed to be a participation in the physiological processes like B-cell guidance to lymph nodes. In 2005, it was shown that CXCL13 was detected in high concentrations in the CSF of patients suffering from acute Lyme neuroborreliosis (1). After invasion into the subarachnoid space, B. burgdorferi induces the release of CXCL13 into the CSF by the mononuclear cells. Subsequently, B cells are recruited to the site of infection, leading to the B-cell-enriched CSF pleocytosis, characteristic to Lyme neuroborreliosis. This lead to the hypothesis that CXCL13 concentration in the CSF could be a promising diagnostic marker for Lyme neuroborreliosis. In line with this hypothesis, initial clinical studies reported very high sensitivities. Moreover, elevated CXCL13 levels are detectable early in the disease process, days to weeks before the antibody production starts. The concentration of this marker rapidly declines after the initiation of antibiotic therapy (2).

Rupprecht et al. performed meta-analysis to evaluate overall diagnostic accuracy of CSF CXCL13 in Lyme neuroborreliosis. A search of PubMed and Web of Science yielded in 18 studies. This meta-analysis suggests that CSF CXCL13 is a readily applicable, reliable diagnostic biomarker for acute Lyme neuroborreliosis (2).

Haglund et al. evaluated and compared the semi-quantitative, cassette-based ReaScan CXCL13 assay with the quantitative recomBead CXCL13 assay. The agreement between the two methods waws 87%. The recomBead assay had a higher sensitivity, while the specificity was higher using ReaScan assay (3). 

CXCL13 has shown to be a useful and reliable test in addition to serology for the diagnosis of the acute Lyme neuroborreliosis. 

Key Points:

  • CXCL13 concentration in the CSF can be a useful diagnostic marker for Lyme neuroborreliosis.
  • CXCL13 is elevated in the CSF of patients with very early Lyme neuroborreliosis where the sensitivity of antibody tests may be low.
  • The concentration of CXCL13 decreases with the initiation of antimicrobial treatment.

References:

  1. Rupprecht TA, Pfister HW, Angele B, Kastenbauer S, Wilske B, Koedel U. The chemokine CXCL13 (BLC): a putative diagnostic marker for neuroborreliosis. Neurology. 2005 Aug 9;65(3):448-50. Doi: 10.1212/01.wnl.0000171349.06645.79. PMID: 16087912.
  2. Rupprecht TA, Manz KM, Fingerle V, Lechner C, Klein M, Pfirrmann M, Koedel U. Diagnostic value of cerebrospinal fluid CXCL13 for acute Lyme neuroborreliosis. A systematic review and meta-analysis. Clin Microbiol Infect. 2018 Dec;24(12):1234-1240. doi: 10.1016/j.cmi.2018.04.007. Epub 2018 Apr 16. PMID: 29674128.
  3. Haglund, S., Lager, M., Gyllemark, P. et al. CXCL13 in laboratory diagnosis of Lyme neuroborreliosis—the performance of the recomBead and ReaScan CXCL13 assays in human cerebrospinal fluid samples. Eur J Clin Microbiol Infect Dis 41, 175–179 (2022). doi.org/10.1007/s10096-021-04350-y.

Co-author(s):
Johann Sellner, Neurologie und Multiple Sklerose Zentrum, Landesklinikum Mistelbach - Gänserndorf

Publish on behalf of the Scientific Panel on Infectious diseases

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