Affiliations: Division of Pediatric Critical Care Medicine and Center for Lung Biology, Seattle Children's Hospital and University of Washington School of Medicine, Seattle, WA, USA | Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA | Division of Pulmonology, Allergy and Immunology, and Critical Care, Riley Hospital for Children, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA | Division of Pediatric Critical Care Medicine, Morgan Stanley Children's Hospital, New York-Presbyterian Hospital, Columbia University College of Physicians and Surgeons, New York, NY, USA
Note:  Corresponding author: Derek S. Wheeler, MD, MMM Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. Tel.: +1 513 636 4259; Fax: +1 513 636 4267; E-mail: [email protected]
Abstract: Extracellular heat shock protein 72 (Hsp72) is an endogenous danger signal and potential biomarker for critical illness in children. We hypothesized that elevated levels of extracellular Hsp72 in the cerebrospinal fluid (CSF) of children with suspected meningitis could predict bacterial meningitis. We measured extracellular Hsp72 levels in the CSF of 31 critically ill children with suspected meningitis via a commercially available enzyme-linked immunosorbent assay. Fourteen had bacterial meningitis based on CSF pleocytosis and bacterial growth in either blood or CSF culture. Seventeen children with negative cultures comprised the control group. CSF Hsp72 was significantly elevated in children with bacterial meningitis compared to controls. Importantly, CSF Hsp72 levels did not correlate with the CSF white blood cell count. On receiver operator characteristic analysis, using a cut-off of 8.1 ng/mL, CSF Hsp72 has a sensitivity of 79% and a specificity of 94% for predicting bacterial meningitis. We therefore conclude that CSF extracellular Hsp72 levels are elevated in critically ill children with bacterial meningitis versus controls. Hsp72 potentially offers clinicians improved diagnostic information in distinguishing bacterial meningitis from other processes.