title: Heparin-binding protein: a diagnostic marker of acute bacterial meningitis.
abstract: BACKGROUND
  The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis.
  
  
  OBJECTIVE
  In this study we investigated whether heparin-binding protein levels in cerebrospinal fluid could be used as a diagnostic marker for acute bacterial meningitis.
  
  
  METHODS
  One prospective and one retrospective patient cohort from two university hospitals in Sweden were analyzed.
  
  
  METHODS
  Cerebrospinal fluid samples were collected from 174 patients with suspected central nervous system infection. Thirty-seven patients with acute community-acquired bacterial meningitis, four patients with neurosurgical bacterial meningitis, 29 patients with viral meningitis or encephalitis, seven patients with neuroborreliosis, and 97 control patients were included.
  
  
  METHODS
  None.
  
  
  RESULTS
  Cerebrospinal fluid samples were analyzed for the concentrations of heparin-binding protein, lactate, protein, glucose, neutrophils, and mononuclear cells. Heparin-binding protein levels were significantly higher (p < .01) in patients with acute bacterial meningitis (median 376 ng/mL, range 12-858 ng/mL) than in patients with viral central nervous system infection (median 4.7 ng/mL, range 3.0-41 ng/mL) or neuroborreliosis (median 3.6 ng/mL, range 3.2-10 ng/mL) or in control patients with a normal cerebrospinal fluid cell count (median 3.5 ng/mL, range 2.4-8.7 ng/mL). In the prospectively studied group, a heparin-binding protein concentration exceeding 20 ng/mL gave a sensitivity of 100%, a specificity of 99.2%, and positive and negative predictive values of 96.2% and 100%, respectively, in diagnosing acute bacterial meningitis. The area under the receiver-operating characteristic curve for heparin-binding protein was 0.994, which was higher than for the other investigated parameters.
  
  
  CONCLUSIONS
  Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.
authors.affiliation: Department of Clinical Sciences, Division of Infection Medicine, Lund University Hospital, Lund, Sweden. adam.linder@med.lu.se
authors.forename: Adam
authors.initials: A
authors.lastname: Linder
authors.forename: Per
authors.initials: P
authors.lastname: Akesson
authors.forename: Magnus
authors.initials: M
authors.lastname: Brink
authors.forename: Marie
authors.initials: M
authors.lastname: Studahl
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
authors.forename: Bertil
authors.initials: B
authors.lastname: Christensson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023181:Antimicrobial Cationic Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001798:Blood Proteins / Q000134:cerebrospinal fluid*; D002352:Carrier Proteins / Q000134:cerebrospinal fluid*; D018792:Encephalitis, Viral / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000382:microbiology; D008587:Meningitis, Viral / Q000134:cerebrospinal fluid / Q000175:diagnosis; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: C062991:AZU1 protein, human; D023181:Antimicrobial Cationic Peptides; D015415:Biomarkers; D001798:Blood Proteins; D002352:Carrier Proteins