Cerebrospinal fluid CXCL13 as a diagnostic marker of neuroborreliosis in children: a retrospective case-control study

Abstract

BackgroundLyme neuroborreliosis (LNB) is a frequent manifestation of Lyme disease in children and its current diagnosis has limitations. The elevation of the chemokine CXCL13 in the cerebrospinal fluid (CSF) of adult patients with LNB has been demonstrated and suggested as a new diagnostic marker. Our aim was to evaluate this marker in the CSF of children with suspected LNB and to determine a CXCL13 cut-off concentration that would discriminate between LNB and other central nervous system (CNS) infections.MethodsFor this single-center retrospective case-control study we used a diagnostic-approved ELISA to measure CXCL13 concentrations in the CSF of 185 children with LNB suspicion at presentation. Patients were classified into definite LNB (cases), non-LNB (controls with other CNS affections), and possible LNB. A receiver-operating characteristic curve was generated by comparison of cases and controls.ResultsCXCL13 was significantly elevated in the CSF of 53 children with definite LNB (median 774.7 pg/ml) compared to 91 control patients (median 4.5 pg/ml, p < 0.001). A cut-off of 55 pg/ml resulted in a sensitivity of 96.7% and a specificity of 98.1% for the diagnosis of definite LNB and the test exhibited a diagnostic odds ratio of 1525.3. Elevated CSF CXCL13 levels were also detected in three controls with viral meningitis (enterovirus n = 1, varicella-zoster virus n = 2) while other CNS affections such as idiopathic facial palsy did not lead to CXCL13 elevation. Of the 41 patients with possible LNB, 27% had CXCL13 values above the cut-off of 55 pg/ml (median 16.7 pg/ml).ConclusionsCSF CXCL13 is highly elevated in children during early LNB as previously shown in adults. CXCL13 is a highly sensitive and specific marker that helps to differentiate LNB from other CNS affections in children.

Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance

“…The aims of pediatric studies included a reduction in mortality rates and control of the spread of infectious diseases. These studies have proven that CXCL13 concentration in the CSF of pediatric patients is significantly increased in neuroborreliosis compared to non-neuroborreliosis individuals [8,9,44,47]. One study revealed that differences in CXCL13 levels between children with neuroborreliosis and those with other conditions were statistically significant, although relatively small [45].…”

“…The pathogenesis of neuroborreliosis involves a complex immune response due to Borrelia burgdorferi sensu lato, resulting in the specific activation of B lymphocytes. There is a greater number of activated B cells in the CSF than in the blood, and the percentage of B-cells in the CSF of patients with neuroborreliosis increases up to 80% [47]. One of the key regulators of B-cells is CXCL13, whose concentration may be elevated at the onset of neuroborreliosis, before the synthesis of intrathecal Borrelia burgdorferi sensu lato antibodies occurs [47].…”

“…There is a greater number of activated B cells in the CSF than in the blood, and the percentage of B-cells in the CSF of patients with neuroborreliosis increases up to 80% [47]. One of the key regulators of B-cells is CXCL13, whose concentration may be elevated at the onset of neuroborreliosis, before the synthesis of intrathecal Borrelia burgdorferi sensu lato antibodies occurs [47]. Several studies have demonstrated a strong association between CXCL13 and specific neuroinflammatory diseases when compared to non-inflammatory central nervous system disorders or asymptomatic HIV infection.…”

“…Moreover, CXCL13 appears to be detectable earlier than antibodies against Borrelia burgdorferi sensu lato [50]. All children with possible neuroborreliosis, pleocytosis, facial nerve palsy, and/or anti-Borrelia burgdorferi sensu lato antibodies have been found to have increased levels of CXCL13 in the CSF [8,47]. Some authors have demonstrated that serum and CSF CXCL13 levels are elevated in all patients (adults and children) with definite acute neuroborreliosis [27,48].…”

Pediatric stroke related to Lyme neuroborreliosis: Data from the Swiss NeuroPaediatric Stroke Registry and literature review

“…It might prove useful in atypical situations (high suspicion index but negative serology). [31,35] The treatment of choice is IV Ceftriaxone (2 g/day or 50-75 mg/kg/day) for a duration of 14 to 21 days depending on the type of symptoms and their duration (early versus late neuroborreliosis). Oral Doxicyline might be a safe and efficient alternative but is reserved for children above eight years.…”