CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation

Abstract

BackgroundLaboratory diagnosis of Lyme neuroborreliosis (LNB) is partly based on the detection of intrathecal Borrelia burgdorferi–specific antibody production (increased antibody index (AI)). However, AI can be negative in patients with early LNB and, conversely, can remain elevated for months after antibiotic treatment. Recent studies suggested that the chemokine CXCL13 in the cerebrospinal fluid (CSF) is a biomarker for active LNB. Also, CSF neopterin-level determination has been used to assess the degree of neuroinflammation in a wide variety of diseases.MethodsCXCL13 concentrations were analyzed in CSF samples of 366 retrospectively identified individuals. The samples represented pretreatment LNB (38 patients), non-LNB comparison patients, tick-borne encephalitis, central nervous system (CNS) varicella zoster virus infection, CNS herpes simplex virus infection, CNS HHV6 infection, CNS enterovirus infection, and untreated neurosyphilis. The panel included also samples from patients with multiple sclerosis and other neuroinflammatory conditions. Of the LNB patients, 24 posttreatment CSF samples were available for CXCL13 analysis. Neopterin concentrations were determined in a subset of these samples.ResultsThe CXCL13 concentrations in CSF samples of untreated LNB patients were significantly higher (median, 6,480 pg/ml) than the concentrations in the non-LNB group (median, <7.8 pg/ml), viral CNS infection samples (median, <7.8 pg/ml), or samples from patients with noninfectious neuroinflammatory conditions (median, <7.8 pg/ml). The use of cut-off 415 pg/ml led to a sensitivity of 100% and specificity of 99.7% for the diagnosis of LNB in these samples. CSF CXCL13 median concentrations declined significantly from 16,770 pg/ml before to 109 pg/ml after the treatment.CSF neopterin concentration was significantly higher among the untreated LNB patients than in the non-LNB group. The use of neopterin concentration 10.6 nM as the cut-off led to a sensitivity of 88.6% and a specificity of 65.0% for the diagnosis of LNB. The CSF neopterin concentrations decreased statistically significantly with the treatment.ConclusionsThese results clearly indicate that highly elevated CSF CXCL13 levels are strongly associated with untreated LNB. CXCL13 outperformed neopterin and appears to be an excellent biomarker in differentiating LNB from viral CNS infections and from other neuroinflammatory conditions.

CXCL13 levels are more increased in cerebrospinal fluid and plasma of patients with acute infectious than in non-infectious diseases of the central nervous system

“…Polymerase chain reaction techniques demonstrated that CXCL13 is produced in case of active demyelinating diseases, and not in inactive or chronic lesions within the CNS of patients who have never had neuro-logical diseases. Therefore, CXCL13 is one of the factors that attract and arrest B and T cells, which play a role in the inflammatory processes of neuroinflammatory disorders [1,3,6,19]. We did not include in our study patients suffering from demyelinating neurological diseases.…”

“…In a previous study, a significant correlation was found between mononuclear cells and CSF CXCL13 chemokine. The reason for this correlation is still unknown [3].…”

“…Hence, it has also been proposed as a specific diagnostic marker for this condition. High concentrations of CXCL13 chemokine can be detected in the CSF several days before anti-Borrelia burgdorferi (Bb) antibodies occur [3].…”

“…Patients with multiple sclerosis (MS), Lyme neuroborreliosis (LNB), and other autoimmune diseases present high levels of CXCL13 expression in the cerebrospinal fluid (CSF), which correlate with the number of B and T cells in the CSF and intrathecal immunoglobulin production [2][3][4].…”

The diagnostic role and dynamic changes in cerebrospinal fluid neopterin during treatment of patients with primary central nervous system lymphoma

“…In addition, diagnosis based on brain biopsy specimens obtained after craniotomy or stereotactic brain biopsy can result in a failure rate of approximately 10%‐35% in patients with rapidly deteriorating neurological conditions 10. Cytology or tumor biomarkers in the cerebrospinal fluid (CSF) are important for diagnosis and differential diagnosis of PCNSL, especially for patients who are not suitable for brain biopsy 6, 11. Identification of diagnostic biomarkers may help in the early diagnosis and treatment of PCNSL and improve patient prognosis.…”