title: Cerebrospinal Fluid Markers of Macrophage and Lymphocyte Activation After Traumatic Brain Injury in Children.
abstract: OBJECTIVE
  The magnitude and role of the cellular immune response following pediatric traumatic brain injury remains unknown. We tested the hypothesis that macrophage/microglia and T-cell activation occurs following pediatric traumatic brain injury by measuring cerebrospinal fluid levels of soluble cluster of differentiation 163 and ferritin and soluble interleukin-2 receptor α, respectively, and determined whether these biomarkers were associated with relevant clinical variables and outcome.
  
  
  METHODS
  Retrospective analysis of samples from an established, single-center cerebrospinal fluid bank.
  
  
  METHODS
  PICU in a tertiary children's hospital.
  
  
  METHODS
  Sixty-six pediatric patients after severe traumatic brain injury (Glasgow Coma Scale score < 8) who were 1 month to 16 years old and 17 control patients who were 1 month to 14 years old.
  
  
  METHODS
  None.
  
  
  RESULTS
  Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor α were determined by enzyme-linked immunosorbent assay at two time points (t1 = 17 ± 10 hr; t2 = 72 ± 15 hr) for each traumatic brain injury patient. Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor α after traumatic brain injury were compared with controls and analyzed for associations with age, patient sex, initial Glasgow Coma Scale score, diagnosis of abusive head trauma, the presence of hemorrhage on CT scan, and Glasgow Outcome Scale score. Cerebrospinal fluid level of soluble cluster of differentiation 163 was increased in traumatic brain injury patients at t2 versus t1 and controls (median, 95.4 ng/mL [interquartile range, 21.8-134.0 ng/mL] vs 31.0 ng/mL [5.7-77.7 ng/mL] and 27.8 ng/mL [19.1-43.1 ng/mL], respectively; p < 0.05). Cerebrospinal fluid level of ferritin was increased in traumatic brain injury patients at t2 and t1 versus controls (8.3 ng/mL [<7.5-19.8 ng/mL] and 8.9 ng/mL [<7.5-26.7 ng/mL] vs <7.5 ng/mL below lower limit of detection, respectively; p < 0.05). Cerebrospinal fluid levels of soluble interleukin-2 receptor α in traumatic brain injury patients at t2 and t1 were not different versus controls. Multivariate regression revealed associations between high ferritin and age 4 years or younger, lower Glasgow Coma Scale score, abusive head trauma, and unfavorable Glasgow Outcome Scale score.
  
  
  CONCLUSIONS
  Children with traumatic brain injury demonstrate evidence for macrophage activation after traumatic brain injury, and in terms of cerebrospinal fluid ferritin, this appears more prominent with young age, initial injury severity, abusive head trauma, and unfavorable outcome. Further study is needed to determine whether biomarkers of macrophage activation may be used to discriminate between aberrant and adaptive immune responses and whether inflammation represents a therapeutic target after traumatic brain injury.
authors: 1Department of Pediatrics, University of Iowa, Iowa City, IA. 2Department of Pediatrics, University of California San Diego, La Jolla, CA. 3Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. 4Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA. 5The Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA. 6Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA. 7Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA. 8Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA. 9Department of Environmental and Occupational Health, University of Pittsburgh School of Medicine, Pittsburgh, PA. 10Clinical and Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors: Elizabeth
authors: E
authors: Newell
authors: David K
authors: DK
authors: Shellington
authors: Dennis W
authors: DW
authors: Simon
authors: Michael J
authors: MJ
authors: Bell
authors: Patrick M
authors: PM
authors: Kochanek
authors: Keri
authors: K
authors: Feldman
authors: Hülya
authors: H
authors: Bayir
authors: Rajesh K
authors: RK
authors: Aneja
authors: Joseph A
authors: JA
authors: Carcillo
authors: Robert S B
authors: RS
authors: Clark
mesh_terms: D000293:Adolescent; D000367:Age Factors; D015703:Antigens, CD / Q000134:cerebrospinal fluid*; D015214:Antigens, Differentiation, Myelomonocytic / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001930:Brain Injuries / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002649:Child Abuse / Q000175:diagnosis; D002675:Child, Preschool; D005260:Female; D005293:Ferritins / Q000134:cerebrospinal fluid*; D015600:Glasgow Coma Scale; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D017628:Microglia / Q000276:immunology; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D005293:Ferritins