title: Decreased Epidermal Growth Factor (EGF) Associated with HMGB1 and Increased Hyperactivity in Children with Autism.
abstract: BACKGROUND
  Autism spectrum disorders (ASDs), characterized by impaired social interactions and deficits in verbal and nonverbal communication, are thought to affect 1 in 88 children in the United States. There is much support for the role of growth factors in the etiology of autism. Recent research has shown that epithelial growth factor (EGF) is decreased in young autistic children (2-4 years of age). This study was designed to determine plasma levels of EGF in an older group of autistic children (mean age 10.6 years) and to correlate these EGF levels with putative biomarkers HGF, uPA, uPAR, GAD2, MPO GABA, and HMGB1, as well as symptom severity of 19 different symptoms.
  
  
  METHODS
  Plasma from 38 autistic children, 11 children with pervasive developmental disorder (PDD-NOS) and 40 neurotypical, age and gender similar controls was assessed for EGF concentration using ELISAs. Severity of 19 symptoms (awareness, expressive language, receptive language, (conversational) pragmatic language, focus/attention, hyperactivity, impulsivity, perseveration, fine motor skills, gross motor skills, hypotonia (low muscle tone), tiptoeing, rocking/pacing, stimming, obsessions/fixations, eye contact, sound sensitivity, light sensitivity, and tactile sensitivity) was assessed and then compared to EGF concentrations.
  
  
  RESULTS
  In this study, we found EGF levels in autistic children and those with PDD-NOS to be significantly lower when compared with neurotypical controls. EGF levels correlated with HMGB1 levels but not the other tested putative biomarkers, and EGF correlated negatively with hyperactivity, gross motor skills, and tiptoeing but not other symptoms.
  
  
  CONCLUSIONS
  These results suggest an association between decreased plasma EGF levels and selected symptom severity. We also found a strong correlation between plasma EGF and HMGB1, suggesting inflammation is associated with decreased EGF.
authors: Hartwick College, Oneonta, NY.
authors: Anthony J
authors: AJ
authors: Russo
keywords: EGF; GABA; HMGB1; PDD; autism; symptom severity
references: Nature. 1995 Jul 27;376(6538):337-41
references: 7630400
references: Nat Rev Neurol. 2011 Jan;7(1):31-40
references: 21135885
references: Brain Behav Immun. 2011 Jan;25(1):40-5
references: 20705131
references: Mol Neurobiol. 1999 Oct-Dec;20(2-3):157-83
references: 10966120
references: Biol Psychiatry. 2007 Aug 1;62(3):267-9
references: 17123472
references: J Autism Dev Disord. 2011 Feb;41(2):237-41
references: 20544265
references: Biomark Insights. 2009 Nov 27;4:181-90
references: 20029653
references: J Immunol. 2008 Apr 1;180(7):5067-74
references: 18354232
references: J Anat. 2003 Jul;203(1):1-19
references: 12892403
references: Neuroscience. 2004;128(1):155-62
references: 15450362
references: Exp Neurol. 2010 Jan;221(1):129-35
references: 19853606
references: J Neuroimmunol. 2009 Feb 15;207(1-2):111-6
references: 19157572
references: J Biol Chem. 1992 Oct 25;267(30):21277-80
references: 1383221
references: Brain Behav Immun. 2010 Jan;24(1):64-71
references: 19666104
references: Nat Med. 2010 Apr;16(4):413-9
references: 20348922
references: Physiol Genomics. 2012 Feb 27;44(4):268-80
references: 22214601
references: Expert Rev Dermatol. 2008 Oct;3(5):525-527
references: 19649143
references: J Biol Chem. 1966 Mar 25;241(6):1355-8
references: 4222879
references: Biochem Biophys Res Commun. 2007 Sep 7;360(4):715-20
references: 17626784
references: J Neurosci. 1996 Apr 15;16(8):2649-58
references: 8786441
references: Mol Psychiatry. 2011 May;16(5):478-90
references: 20938434
references: N Engl J Med. 2003 Jul 24;349(4):395-7
references: 12878748
references: Biochim Biophys Acta. 2010 Jan-Feb;1799(1-2):164-70
references: 19914413
references: J Immunol. 2009 May 1;182(9):5800-9
references: 19380828
references: Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2580-5
references: 20133656
references: Ann Neurol. 2005 Jan;57(1):67-81
references: 15546155
references: Prog Brain Res. 2004;146:387-401
references: 14699975
references: J Immunol. 2005 Oct 1;175(7):4745-53
references: 16177122
references: Nat Rev Neurosci. 2008 Jul;9(7):557-68
references: 18568015
references: Autism Res Treat. 2012;2012:205362
references: 22937258