Neuroimmunomodulators in Neuroborreliosis and Lyme Encephalopathy

Abstract

CSF CXCL13 is a sensitive and specific marker of neuroborreliosis in individuals with Borrelia-specific intrathecal antibody production. However, it does not distinguish individuals strongly suspected of having neuroborreliosis, but lacking confirmatory intrathecal antibodies, from those with other neuroinflammatory conditions. Patients with mild cognitive symptoms occurring during acute Lyme disease, and/or after appropriate treatment, have normal CSF but elevated serum levels of T-helper 17 markers and T-cell growth factors, which are also elevated in patients without Lyme disease but with similar symptoms. In the absence of CSF abnormalities, neurobehavioral symptoms appear to be associated with systemic inflammation, not CNS infection or inflammation, and are not specific to Lyme disease.

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].…”

“…Such results also suggest that CXCL13 levels can be helpful in distinguishing the activity and acuteness of the current infection from previous infections [5,34,[37][38][39][40]. Levels of the chemokine in possible neuroborreliosis with negative specific antibodies has been found not to differ from other neurological conditions, e.g., multiple sclerosis, viral meningitis, neurosyphilis, or lupus [41].…”

“…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.…”

Limitations and Confusing Aspects of Diagnostic Testing for Neurologic Lyme Disease in the United States

“…These findings indicate that reliance on NAATs for routine diagnosis of CNSLD should be avoided, and that such testing should be considered an adjunct methodology only. Additionally, detection of CXCL13, a B cell-attracting chemokine, in CSF has been proposed as a biomarker to support the diagnosis of CNSLD (10)(11)(12). However, although CXCL13 CSF levels are elevated in patients with CNSLD, the presence of this chemokine does not provide sufficient specificity to distinguish CNSLD from other neuroinflammatory syndromes, and levels can rapidly fall below the cutoff threshold if antibiotic therapy is initiated prior to CSF collection (10)(11)(12)(13).…”