Abstract
Background The aim of this study was to evaluate the diagnostic performance of cerebrospinal fluid (CSF) free light chains (FLCs) in the diagnosis of Lyme neuroborreliosis (LNB). Methods Serum and CSF levels of κ- and λ-FLC, albumin and total concentration of immunoglobulin M (IgM) were determined together with CSF chemokine CXCL13 in 23 patients with definite LNB, 35 inflammatory neurological disease control (INDC) and 18 non-inflammatory control (NIC) patients. Indices and intrathecal fractions (IFs) of FLC and IgM were calculated. Results Significant differences in FLC indices and IFs were found between the LNB group and both control groups, p ≤ 0.007. Sensitivity of intrathecal κ- and λ-FLC synthesis reached 78%-87% in LNB patients with a specificity of 94%-100% in NIC patients, whereas specificity in INDC patients was 69%. The corresponding frequencies of positive results for IF and index of IgM and CSF CXCL13 in these three diagnostic groups were 74%-96% in LNB patients, 0% in NIC patients and 3%-6% in INDC patients at the chosen cut-off levels. Conclusions The findings of this study show a moderate to high sensitivity of CSF κ- and λ-FLC in LNB patients with a high specificity in NIC patients. However, overlap in CSF κ- and λ-FLC levels between LNB and INDC patients calls for caution in the interpretation and limits the diagnostic usefulness in the LNB diagnosis. CSF CXCL13 appears to be the most valuable additional biomarker of LNB aside from routine parameters such as CSF pleocytosis and anti-Borrelia antibody index.
Highlights
Lyme borreliosis (LB) is the most common known tickborne infection in both Europe and North America, and is caused by spirochetes of the Borrelia burgdorferi sensu lato complex [1, 2]
In order to compare the ability of different parameters to discriminate between diagnostic groups, cut-off values and areas under curve (AUC) with 95% confidence intervals (CI) were calculated using the groups Lyme neuroborreliosis (LNB) and non-inflammatory control (NIC) (Table 1) in receiver-operating characteristic (ROC) analyses using MedCalc, version 18.6
In some contrast to the findings by Hegen et al, in our study we show a considerable overlap in levels of κ- and λ-free light chains (FLCs) indices as well as intrathecal fractions (IFs) between LNB patients and inflammatory control patients including a variety of relevant clinical conditions. κ- and λ-FLC levels above the cut-off were found in 31% of the patients in the inflammatory neurological disease control (INDC) group, reducing specificity to 69%, limiting the diagnostic usefulness of κ- and λ-FLC in LNB diagnostics
Summary
Lyme borreliosis (LB) is the most common known tickborne infection in both Europe and North America, and is caused by spirochetes of the Borrelia burgdorferi sensu lato complex [1, 2]. Already some 20 years ago, it was shown that the total concentration of immunoglobulin M (IgM) in CSF is elevated in early LNB [12]. This has been confirmed in two more recent studies expressed as elevated total IgM index. Methods: Serum and CSF levels of κ- and λ-FLC, albumin and total concentration of immunoglobulin M (IgM) were determined together with CSF chemokine CXCL13 in 23 patients with definite LNB, 35 inflammatory neurological disease control (INDC) and 18 non-inflammatory control (NIC) patients. Overlap in CSF κ- and λ-FLC levels between LNB and INDC patients calls
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