Chemokines CXCL10, CXCL11, and CXCL13 in acute disseminated encephalomyelitis, non-polio enterovirus aseptic meningitis, and neuroborreliosis: CXCL10 as initial discriminator in diagnostic algorithm?

Abstract

We investigated potential diagnostic usefulness of serum and cerebrospinal fluid (CSF) concentrations of chemokines CXCL10, CXCL11, and CXCL13 in pediatric patients with acute disseminated encephalomyelitis (ADEM) (n = 23), non-polio enterovirus aseptic meningitis (NPEV AM) (n = 20), and neuroborreliosis (NB) (n = 21) and children with acute infectious diseases with neurological symptoms but with excluded neuroinfection/neuroinflammation (controls, n = 20). CSF levels of CXCL10 and CXCL11 were higher in patients with NPEV AM than those in other children, and CXCL10 levels showed a high discriminative potential (area under the receiver operating characteristic curve, ROC, 0.982) with high specificity and sensitivity (both 95%). CSF levels of CXCL13 were higher in NB patients than those in other children; however, discriminative potential (area under ROC curve 0.814) and diagnostic properties were moderate (sensitivity 67%, specificity 97%). Data suggest usefulness of chemokine quantification as a diagnostic aid in children with suspected ADEM, NPEV AM, or NB.

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

“…However, most studies measuring CXCL13 using ELISA and lateral flow (LFA) methods have shown elevated CXCL13 circulation levels in the CSF of patients with acute neuroborreliosis compared to other tested groups. Results of the available studies suggest its very high diagnostic value and report its high sensitivity and specificity [5][6][7][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. These studies are in agreement with a meta-analysis performed by Yang J. et al, who confirmed that CXCL13 has a high sensitivity and specificity for diagnosing neuroborreliosis [68].…”

“…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]. CXCL13 also confirmed the diagnosis of possible neuroborreliosis in 100% of patients, indicating a higher diagnostic sensitivity than intrathecal-specific antibodies synthesis [27,48].…”

“…Neuroborreliosis CSF CXCL13 levels are highly elevated in NB compared to healthy and other non-inflammatory CNS diseases [5][6][7][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] CSF CXCL13 levels are significantly elevated in NB in comparison to NS [9,10,12] CSF CXCL13 concentrations are elevated in acute and possible NB with positive specific antibodies against Borrelia burgdorferi [5,34,[37][38][39][40] CSF CXCL13 concentrations correlate with WBC count and disease activity [41,42] CSF CXCL13 concentrations correlate better with pleocytosis than with CSF-specific antibodies [5,34,[37][38][39][40] CSF CXCL13 levels are highly elevated in NB patients with shorter disease duration [41,42] CSF CXCL13 levels are markedly elevated before treatment compared to after treatment [7,28,32,…”

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

“…The finding of neutrophil activation in both LNB and EVM is intriguing, since these infections have similarities with respect to both clinical presentation and CSF cellular profile, which may include neutrophil predominance in the early phase [35]. Several studies have de facto shown the presence of neutrophil-activating cytokines and chemokines in the CSF samples of patients with LNB [36][37][38][39] and EVM [40,41], and the production of neutrophil chemo-attractants, such as CXCL1, CXCL8 and CXCL10 after in vitro stimulation of neuronal cells in response to B. burgdorferi spirochaetes [42]. Thus, there appears to be a prerequisite for neutrophil recruitment into the CNS in infections caused by B. burgdorferi and enterovirus.…”

“…The chemokine CXCL10, also called interferon (IFN) γ-inducible protein 10 (IP-10), is produced by innate immune cells, such as neutrophils, and it stimulates chemotaxis of mononuclear cells into the CNS in response to meningitis/encephalitis caused by, for instance, enterovirus [43], B. burgdorferi [44], and TBE virus [45]. Furthermore, IP-10 has been proposed as a potential discriminator between bacterial and viral CNS infections [41]. Interestingly, CXCL10 was particularly increased in the EVM group, in which the proportion of polynuclear cells was highest.…”