ABSTRACT
BACKGROUND: Lyme neuroborreliosis (LNB) is characterized by cerebrospinal fluid (CSF) inflammation with several cytokines/chemokines and B-lymphocytes. Clinically, LNB in children may be difficult to discriminate from non-Lyme aseptic meningitis (NLAM). We aimed to identify CSF cytokine/chemokine patterns in children with LNB, NLAM and controls and elucidate the diagnostic value of these cytokines/chemokines alone or in combination to discriminate between LNB and NLAM. METHODS: Children with symptoms suggestive of LNB were included prospectively and categorized as LNB, NLAM or controls (no pleocytosis). Cytokines/chemokines in CSF were measured by multiplex bead assays and levels were compared between the three groups by nonparametric statistical tests. Previous results from the same children on the established biomarker, CXCL13, were included in the statistical analyses. The diagnostic properties of cytokines/chemokines to discriminate between LNB and NLAM were determined by receiver operating characteristic curve analyses with estimates of area under curve (AUC). To explore diagnostic properties of combinations of cytokines/chemokines, prediction models based on logistic regression were used. RESULTS: We included 195 children with LNB (n = 77), NLAM (n = 12) and controls (n = 106). Children with LNB had higher CSF levels of CCL19, CCL22 and CXCL13 compared to NLAM and controls, whereas INFγ was higher in NLAM than in LNB and controls. CXCL13 was the superior single cytokine/chemokine to discriminate LNB from NLAM (AUC 0.978). The combination CXCL13/CCL19 (AUC 0.992) may possibly improve the specificity for LNB, especially for children with moderate CXCL13 levels. CONCLUSIONS: The intrathecal immune reaction in LNB is characterized by B cell associated chemokines. Whether the combination CXCL13/CCL19 further improves discrimination between LNB and NLAM beyond the diagnostic improvements by CXCL13 alone needs to be tested in new studies.
ABSTRACT
Background: The B-lymphocyte chemokine CXCL13 is increasingly considered as a useful early phase diagnostic marker of Lyme neuroborreliosis (LNB). However, the large variation in level of CXCL13 in the cerebrospinal fluid (CSF) observed in LNB patients is still unexplained. We aimed to identify factors associated with the level of CXCL13 in children with LNB, possibly improving the interpretation of CXCL13 as a diagnostic marker of LNB. Methods: Children with confirmed and probable LNB were included in a prospective study on CXCL13 in CSF as a diagnostic marker of LNB. The variables age, sex, facial nerve palsy, generalized inflammation symptoms (fever, headache, neck-stiffness and/or fatigue), duration of symptoms, Borrelia antibodies in CSF, Borrelia antibody index (AI), CSF white blood cells (WBC), CSF protein and detection of the genospecies Borrelia garinii by PCR were included in simple and multivariable regression analyses to study the associations with the CXCL13 level. Results: We included 53 children with confirmed and 17 children with probable LNB. CXCL13 levels in CSF were positively associated with WBC, protein and Borrelia antibodies in CSF in both simple and multivariable analyses. We did not find any associations between CXCL13 and age, sex, clinical symptoms, duration of symptoms, AI or the detection of Borrelia garinii. Conclusions: High levels of CSF CXCL13 are present in the early phase of LNB and correlate with the level of CSF WBC and protein. Our results indicate that CSF CXCL13 in children evaluated for LNB can be interpreted independently of clinical features or duration of symptoms.
