title: Cerebrospinal fluid CXCL13 in Lyme neuroborreliosis and asymptomatic HIV infection.
abstract: BACKGROUND
  It has been suggested that cerebrospinal fluid (CSF) CXCL13 is a diagnostic marker of Lyme neuroborreliosis (LNB), as its levels have been shown to be significantly higher in LNB than in several other CNS infections. Levels have also been shown to decline after treatment with intravenous ceftriaxone, but levels after treatment with oral doxycycline have previously not been studied. Like Borrelia burgdorferi, HIV also has neurotropic properties. Elevated serum CXCL13 concentrations have been reported in HIV patients, but data on CSF levels are limited.
  
  
  METHODS
  We longitudinally analysed CSF CXCL13 concentrations in 25 LNB patients before and after oral doxycycline treatment. Furthermore, we analysed CSF CXCL13 concentrations in 16 untreated LNB patients, 27 asymptomatic untreated HIV-1 infected patients and 39 controls with no signs of infectious or inflammatory disease.
  
  
  RESULTS
  In the longitudinal LNB study, initially high CSF CXCL13 levels declined significantly after doxycycline treatment, which correlated to a decreased CSF mononuclear cell count. In the cross-sectional study, all the LNB patients had CSF CXCL13 levels elevated above the lowest standard point of the assay (7.8 pg/mL), with a median concentration of 500 pg/mL (range 34-11,678). Of the HIV patients, 52% had elevated CSF CXCL13 levels (median 10 pg/mL, range 0-498). There was a clear overlap in CSF CXCL13 concentrations between LNB patients and asymptomatic HIV patients. All but one of the 39 controls had CSF CXCL13 levels below 7.8 pg/mL.
  
  
  CONCLUSIONS
  We confirm previous reports of highly elevated CSF CXCL13 levels in LNB patients and that these levels decline after oral doxycycline treatment. The same pattern is seen for CSF mononuclear cells. CSF CXCL13 levels are elevated in neurologically asymptomatic HIV patients and the levels overlap those of LNB patients. The diagnostic value of CSF CXCL13 in LNB remains to be established.
authors.affiliation: Department of Infectious Medicine, Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. daniel.bremell@infect.gu.se
authors.forename: Daniel
authors.initials: D
authors.lastname: Bremell
authors.forename: Niklas
authors.initials: N
authors.lastname: Mattsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Edsbagge
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Ulf
authors.initials: U
authors.lastname: Andreasson
authors.forename: Carsten
authors.initials: C
authors.lastname: Wikkelsö
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Lars
authors.initials: L
authors.lastname: Hagberg
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D054382:Chemokine CXCL13 / Q000134:cerebrospinal fluid*; D003430:Cross-Sectional Studies; D004318:Doxycycline / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005029:Ethylenediamines / Q000134:cerebrospinal fluid; D005260:Female; D015658:HIV Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D006801:Humans; D008137:Longitudinal Studies; D020852:Lyme Neuroborreliosis / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000134:cerebrospinal fluid; D012372:ROC Curve; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C088402:4-(3,5-dimethyl-3-aza-5-mercaptohexyl)-6,6-dimethyl-2-thiomorpholinone; D000900:Anti-Bacterial Agents; C110663:CXCL13 protein, human; D054382:Chemokine CXCL13; D005029:Ethylenediamines; D009025:Morpholines; D004318:Doxycycline