Heparin-binding protein: a diagnostic marker of acute bacterial meningitis

Crit Care Med. 2011 Apr;39(4):812-7. doi: 10.1097/CCM.0b013e318206c396.

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.

Design: One prospective and one retrospective patient cohort from two university hospitals in Sweden were analyzed.

Setting and patients: 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.

Interventions: None.

Measurements and main 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.

Conclusion: Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimicrobial Cationic Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Blood Proteins / cerebrospinal fluid*
  • Carrier Proteins / cerebrospinal fluid*
  • Encephalitis, Viral / cerebrospinal fluid
  • Encephalitis, Viral / diagnosis
  • Female
  • Humans
  • Leukocyte Count
  • Male
  • Meningitis, Bacterial / cerebrospinal fluid
  • Meningitis, Bacterial / diagnosis*
  • Meningitis, Bacterial / microbiology
  • Meningitis, Viral / cerebrospinal fluid
  • Meningitis, Viral / diagnosis
  • Middle Aged
  • Prospective Studies
  • ROC Curve
  • Retrospective Studies
  • Statistics, Nonparametric
  • Young Adult

Substances

  • AZU1 protein, human
  • Antimicrobial Cationic Peptides
  • Biomarkers
  • Blood Proteins
  • Carrier Proteins