The chemokine CXCL13 in cerebrospinal fluid in children with Lyme neuroborreliosis

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.

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].…”

“…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].…”

“…Our review offers an updated analysis of studies, including publications by Halperin and Rupprecht et al, which presents an overview of the diagnosis and management of neuroborreliosis and neurosyphilis and whose authors suggest a potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic marker of these two spirochetal infections of the nervous system [2,[5][6][7][8][9][10][11][12][13]. Chemokines, or chemotactic cytokines, are a very important and large group (more than 50) of low molecular weight proteins structurally homologous to cytokines.…”

Neuroborreliosis – clinical presentation – Current state of knowledge

“…The results of the CXCL13 cytokine determination are promising, especially in children who may not develop antibodies or intrathecal synthesis during the short duration of neurological symptoms in early NB. In children with definite NB, the CXCL13 determination allows the diagnosis to be made with a sensitivity of 88% and a specificity of 89%, and in the probable NB concentration of this chemokine was increased in 73% of children, which makes it a complementary diagnostic tool (25). The CXCL13 cytokine is synthesized at high levels in the cerebrospinal fluid in patients infected with B. burgdorferi in the very early stages of the disease (up to 2 weeks), before antibody production.…”

“…It is recommended to observe the child up to a month after tick bite. chemokiny było podwyższone u 73% dzieci, co czyni z niej uzupełniające narzędzie diagnostyczne (25). Cytokina CXCL13 jest syntetyzowana w wysokich stężeniach w płynie mózgowo-rdzeniowym u pacjentów zakażonych B. burgdorferi w bardzo wczesnych stadiach choroby (do 2 tygodni), jeszcze przed produkcją przeciwciał.…”