The Usefulness of Two CXCL13 Assays on Cerebrospinal Fluid for the Diagnosis of Lyme Neuroborreliosis: a Retrospective Study in a Routine Clinical Setting

Abstract

Recent studies have shown elevated levels of the B-cell chemokine (C-X-C motif) ligand 13 (CXCL13) in the cerebrospinal fluid (CSF) of patients with early Lyme neuroborreliosis (LNB). In this retrospective study, we evaluated the diagnostic performance of the Quantikine CXCL13 ELISA (R&D Systems, Inc., MN, USA) and the recom Bead CXCL13 assay (Mikrogen, Neuried, Germany) for the detection of CXCL13 in CSF. All consecutive patients from whom a CSF and a serum sample had been collected between August 2013 and June 2016 were eligible for inclusion. Patients suspected of LNB were classified as definite, possible or non-LNB according to the guidelines of the European Federation of Neurological Societies (EFNS). Due to the limited number of LNB patients in the predefined study period, additional LNB patients were included from outside this period. In total, 156 patients (150 consecutive patients and six additional LNB patients) were included. Seven (4.5%) were classified as definite, eight (5.1%) as possible and 141 (90.4%) as non-LNB patients. Receiver operating characteristic (ROC) curve analysis comparing definite LNB patients with non-LNB patients showed a cut-off value of 85.9 pg/ml for the Quantikine CXCL13 ELISA and 252.2 pg/ml for the recom Bead CXCL13 assay. The corresponding sensitivities were 100% (95% confidence interval [CI]: 100%-100% (for both), the corresponding specificities were 98.6% [95% CI: 96.5%-100%] for the CXCL13 ELISA, and 97.2% [95% CI: 93.6%-100%] for the recom Bead CXCL13 assay, respectively. This study showed that CXCL13 in CSF can be of additional value for the diagnosis of LNB.

Retrospective Evaluation of Various Serological Assays and Multiple Parameters for Optimal Diagnosis of Lyme Neuroborreliosis in a Routine Clinical Setting

“…Therefore, six additional LNB patients were included from outside this period. As the total number of LNB patients included in the current study was comparable to the 15 patients expected to be diagnosed with LNB in the predefined study period, we believe that the cross-sectional design of the study holds as has been discussed in more detail previously ( 45 ). Third, 20.9% of the non-LNB patients were seropositive for Borrelia -specific IgG, whereas the IgG seroprevalence of the Dutch population is 4% to 8% ( 52 ).…”

“…Details with regard to clinical symptoms suggestive for LNB, an alternative diagnosis that ruled out LNB, and test results (i.e., pleocytosis and intrathecal Borrelia -specific antibody synthesis determined by the CSF-serum assays) needed for the classification of patients are shown in Table S2. The number of possible and definite LNB patients in this study differed slightly from that in our previous study ( 45 ), as intrathecal Borrelia -specific antibody synthesis was based on either a consensus strategy (this study) or the IDEIA results (previous study).…”

“…Six additional LNB patients were included from outside the predefined study period, all of whom had taken part in two other studies ( 43 , 44 ). Details on the selection of the 156 patients have already been published, these patients have also been used to evaluate two commercial CSF-CXCL13 assays ( 45 ).…”

“…Indeed, of all the 423 consecutive patients from whom a CSF and serum sample was drawn less than 24 h apart (see Fig. 1 of the previously published manuscript [ 45 ]), 61 (14.4%) were children (age <18 years; data not shown). In contrast, of the 150 consecutive patients that had sufficient patient material and were included in this study (see Fig.…”

“…In addition to intrathecal Borrelia -specific antibody synthesis, the results of other parameters, such as an elevated CSF leucocyte count ( 3 , 14 , 28 ), a dysfunctional blood-CSF barrier ( 3 , 14 ), intrathecal total antibody synthesis with an IgM dominance ( 14 , 28 , 51 ), and elevated CSF-total protein ( 3 , 14 , 28 ) and CSF-CXCL13 levels ( 3 , 28 , 42 , 45 ), can support the diagnosis of LNB. In our study, these findings were confirmed, as all these parameter results were found among definite LNB patients more often than among non-LNB patients.…”