Abstract

Anti-Borrelia antibodies in the cerebrospinal fluid (CSF) are required for definite diagnosis of Lyme neuroborreliosis (LNB). However, children often present with early LNB, and antibody production in the CSF may not be demonstrated. Recent studies have suggested the chemokine CXCL13 to be an early marker for LNB. The aim of the study was to evaluate CXCL13 for laboratory diagnosis in pediatric LNB patients and to evaluate the association with pleocytosis in CSF, clinical features, and recovery. CSF samples were collected from LNB patients, classified as definite LNB (n = 44) or possible LNB (n = 22), and controls classified as non-LNB (n = 102) or other specific diagnoses (n = 23). CSF samples were analyzed with the recomBead CXCL13 assay (Mikrogen Diagnostik, Germany), cut-off 160 pg/mL. CXCL13 was significantly higher in LNB patients compared to controls (p < 0.001). Among LNB patients, 58/66 had elevated CXCL13, and among controls, 111/125 had CXCL13 levels under cut-off (sensitivity 88%, specificity 89%). In LNB patients with pleocytosis but no detectable anti-Borrelia antibodies in CSF (possible LNB), CXCL13 was elevated in 16/22 (73%). A weak correlation between CXCL13 and pleocytosis in CSF was found in LNB patients (Rho = 0.46, p < 0.01), but no differences in CXCL13 levels in relation to specific clinical features. In conclusion, CXCL13 is elevated in CSF in children with LNB, showing acceptable sensitivity and specificity. In patients with possible LNB, CXCL13 was elevated in a majority of cases (73%) and is suggested as a complementary diagnostic tool in pediatric LNB patients. CXCL13 was not associated with specific clinical features or recovery.

Highlights

  • Lyme borreliosis (LB) is a tick-borne infection caused by spirochetes belonging to the Borrelia burgdorferi sensu latoEur J Clin Microbiol Infect Dis (2018) 37:1983–1991 complex [1]

  • These results are consistent with those observed in several previous studies [18,19,20, 22, 28, 29], all supporting the hypothesis that elevated concentrations of CXC motif ligand 13 (CXCL13) in cerebrospinal fluid (CSF) can be used as a marker for Lyme neuroborreliosis (LNB)

  • Our results suggest that CXCL13 could be used to support the LNB diagnosis in patients with clinical manifestations attributable to LNB and pleocytosis in CSF, but no intrathecally produced anti-Borrelia antibodies

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Summary

Introduction

Lyme borreliosis (LB) is a tick-borne infection caused by spirochetes belonging to the Borrelia burgdorferi sensu latoEur J Clin Microbiol Infect Dis (2018) 37:1983–1991 complex [1]. The Borrelia spirochetes are invasive and motile, disseminating through different tissues in the body. These bacteria do not produce any toxins but they activate the host’s immune defense, causing numerous inflammatory responses that in turn generate the symptoms of the disease [3, 4]. Less specific but common symptoms are headache, fatigue, nausea, loss of appetite, or unspecific pain [9]. Since none of these symptoms are pathognomonic for LNB, laboratory tests are needed to confirm the diagnosis [3]

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