title: Identification of a novel biomarker candidate, a 4.8-kDa peptide fragment from a neurosecretory protein VGF precursor, by proteomic analysis of cerebrospinal fluid from children with acute encephalopathy using SELDI-TOF-MS.
abstract: BACKGROUND
  Acute encephalopathy includes rapid deterioration and has a poor prognosis. Early intervention is essential to prevent progression of the disease and subsequent neurologic complications. However, in the acute period, true encephalopathy cannot easily be differentiated from febrile seizures, especially febrile seizures of the complex type. Thus, an early diagnostic marker has been sought in order to enable early intervention. The purpose of this study was to identify a novel marker candidate protein differentially expressed in the cerebrospinal fluid (CSF) of children with encephalopathy using proteomic analysis.
  
  
  METHODS
  For detection of biomarkers, CSF samples were obtained from 13 children with acute encephalopathy and 42 children with febrile seizure. Mass spectral data were generated by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology, which is currently applied in many fields of biological and medical sciences. Diagnosis was made by at least two pediatric neurologists based on the clinical findings and routine examinations. All specimens were collected for diagnostic tests and the remaining portion of the specimens were used for the SELDI-TOF MS investigations.
  
  
  RESULTS
  In experiment 1, CSF from patients with febrile seizures (n = 28), patients with encephalopathy (n = 8) (including influenza encephalopathy (n = 3), encephalopathy due to rotavirus (n = 1), human herpes virus 6 (n = 1)) were used for the SELDI analysis. In experiment 2, SELDI analysis was performed on CSF from a second set of febrile seizure patients (n = 14) and encephalopathy patients (n = 5). We found that the peak with an m/z of 4810 contributed the most to the separation of the two groups. After purification and identification of the 4.8-kDa protein, a 4.8-kDa proteolytic peptide fragment from the neurosecretory protein VGF precursor (VGF4.8) was identified as a novel biomarker for encephalopathy.
  
  
  CONCLUSIONS
  Expression of VGF4.8 has been reported to be decreased in pathologically degenerative changes such as Alzheimer's disease, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, and encephalopathy. Thus, the VGF4.8 peptide might be a novel marker for degenerative brain conditions.
authors.affiliation: Department of Pediatrics, Nippon Medical School, Chiba Hokusoh Hospital, Inzai City, Chiba, Japan. VFF13540@nifty.ne.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Asano
authors.forename: Shinya
authors.initials: S
authors.lastname: Koizumi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takagi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hatori
authors.forename: Kentaroh
authors.initials: K
authors.lastname: Kuwabara
authors.forename: Osamu
authors.initials: O
authors.lastname: Fujino
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fukunaga
mesh_terms: D015415:Biomarkers / Q000134:cerebrospinal fluid; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000134:cerebrospinal fluid*; D065768:Lennox Gastaut Syndrome; D008297:Male; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D040901:Proteomics / Q000379:methods*; D003294:Seizures, Febrile / Q000134:cerebrospinal fluid / Q000378:metabolism; D013036:Spasms, Infantile / Q000134:cerebrospinal fluid*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D015415:Biomarkers; D009414:Nerve Growth Factors; D010446:Peptide Fragments; C510637:VGF protein, human