title: CXCL13 and neopterin concentrations in cerebrospinal fluid of patients with Lyme neuroborreliosis and other diseases that cause neuroinflammation.
abstract: BACKGROUND
  Laboratory 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.
  
  
  METHODS
  CXCL13 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Turku, Finland. jukka.hytonen@utu.fi.
authors.forename: Jukka
authors.initials: J
authors.lastname: Hytönen
authors.forename: Elisa
authors.initials: E
authors.lastname: Kortela
authors.forename: Matti
authors.initials: M
authors.lastname: Waris
authors.forename: Juha
authors.initials: J
authors.lastname: Puustinen
authors.forename: Jemiina
authors.initials: J
authors.lastname: Salo
authors.forename: Jarmo
authors.initials: J
authors.lastname: Oksi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001898:Borrelia / Q000276:immunology; D020805:Central Nervous System Viral Diseases / Q000134:cerebrospinal fluid / Q000150:complications; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid*; D002648:Child; D002675:Child, Preschool; D004660:Encephalitis / Q000134:cerebrospinal fluid / Q000209:etiology* / Q000382:microbiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020852:Lyme Neuroborreliosis / Q000134:cerebrospinal fluid / Q000150:complications* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000134:cerebrospinal fluid*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D019798:Neopterin