CXCL13 concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other neurological disorders determined by Luminex and ELISA

Ticks Tick Borne Dis. 2018 Jul;9(5):1137-1142. doi: 10.1016/j.ttbdis.2018.04.008. Epub 2018 Apr 20.

Abstract

The aims of the study were to determine and compare the concentration of CXCL13 in cerebrospinal fluid (CSF) of patients with Lyme neuroborreliosis (LNB) and various other neurological disorders applying a Luminex based assay and ELISA, and to find factors associated with CXCL13 concentration. CSF samples obtained from four clinically well-defined groups of patients (proven LNB, suspected LNB, tick-borne encephalitis (TBE), and aseptic meningitis/meningoencephalitis other than TBE) - 25 samples per group - were analyzed. The performance of the Luminex recomBead CXCL13 assay (Microgen, Neuried, Germany) and ELISA (Euroimmun, Lübeck, Germany) was assessed by receiver operating characteristics. CXCL13 cut-off values were presented as functions of CSF lymphocyte/monocyte counts. Demographic variables, CSF findings, and history of erythema migrans were assessed as possible predictors for CXCL13 CSF concentrations by a general linear model. The calculated cut-off values determined by the maximum of the Youden index were >131 pg/mL for recomBead and >259 pg/mL for the ELISA. RecomBead showed a sensitivity of 88% (68.8-97.5%) and a specificity of 94% (83.5-98.7%). For the ELISA the corresponding values were 84% (63.9-95.5%) and 98% (89.4-99.9%). The CXCL13 concentration positively correlated with CSF lymphocyte/monocyte count and Borrelia-specific intrathecal antibody index (p < 0.05). High CXCL13 concentrations were only found in the group with proven LNB. CXCL13 levels above cut-off value were established in some patients with viral meningitis/meningoencephalitis but were not detected in patients with suspected LNB without pleocytosis. Applying a linearized cut-off of the CXCL13 concentration in the CSF which is dependent on the CSF cell count is a novel approach in the laboratory diagnosis of LNB.

Keywords: Aseptic meningitis; CXCL13; Cerebrospinal fluid; Lyme neuroborreliosis; Tick-borne encephalitis; recomBead assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bacterial / cerebrospinal fluid
  • Antibodies, Bacterial / immunology
  • Borrelia / immunology*
  • Chemokine CXCL13 / cerebrospinal fluid*
  • Chemokine CXCL13 / immunology
  • Clinical Laboratory Techniques / instrumentation
  • Clinical Laboratory Techniques / methods
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Humans
  • Immunomagnetic Separation / methods
  • Lyme Neuroborreliosis / cerebrospinal fluid
  • Lyme Neuroborreliosis / diagnosis*
  • Lyme Neuroborreliosis / immunology*
  • Lymphocytes / immunology
  • Male
  • Middle Aged
  • Nervous System Diseases / cerebrospinal fluid*
  • Nervous System Diseases / diagnosis
  • ROC Curve
  • Sensitivity and Specificity

Substances

  • Antibodies, Bacterial
  • CXCL13 protein, human
  • Chemokine CXCL13