title: Serum and cerebrospinal fluid immune mediators in children with autistic disorder: a longitudinal study.
abstract: BACKGROUND
  The causes of autism likely involve genetic and environmental factors that influence neurobiological changes and the neurological and behavioral features of the disorder. Immune factors and inflammation are hypothesized pathogenic influences, but have not been examined longitudinally.
  
  
  METHODS
  In a cohort of 104 participants with autism, we performed an assessment of immune mediators such as cytokines, chemokines, or growth factors in serum and cerebrospinal fluid (n= 67) to determine potential influences of such mediators in autism.
  
  
  RESULTS
  As compared with 54 typically developing controls, we found no evidence of differences in the blood profile of immune mediators supportive of active systemic inflammation mechanisms in participants with autism. Some modulators of immune function (e.g., EGF and soluble CD40 ligand) were increased in the autism group; however, no evidence of group differences in traditional markers of active inflammation (e.g., IL-6, TNFα, IL-1β) were observed in the serum. Further, within-subject stability (measured by estimated intraclass correlations) of most analytes was low, indicating that a single measurement is not a reliable prospective indicator of concentration for most analytes. Additionally, in participants with autism, there was little correspondence between the blood and CSF profiles of cytokines, chemokines, and growth factors, suggesting that peripheral markers may not optimally reflect the immune status of the central nervous system. Although the relatively high fraction of intrathecal production of selected chemokines involved in monocyte/microglia function may suggest a possible relationship with the homeostatic role of microglia, control data are needed for further interpretation of its relevance in autism.
  
  
  CONCLUSIONS
  These longitudinal observations fail to provide support for the hypothesized role of disturbances in the expression of circulating cytokines and chemokines as an indicator of systemic inflammation in autism. ClinicalTrials.gov, NCT00298246.
authors.affiliation: Johns Hopkins University School of Medicine, 627 Pathology Bld., 6000 North Wolfe Street, Baltimore, MD 21287 USA.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Pardo
authors.affiliation: Pediatrics and Developmental Neuroscience, National Institute of Mental Health, Bethesda, MD USA.
authors.forename: Cristan A
authors.initials: CA
authors.lastname: Farmer
authors.affiliation: Pediatrics and Developmental Neuroscience, National Institute of Mental Health, Bethesda, MD USA.
authors.forename: Audrey
authors.initials: A
authors.lastname: Thurm
authors.affiliation: Yale School of Public Health, Yale University, New Haven, CT USA.
authors.forename: Fatma M
authors.initials: FM
authors.lastname: Shebl
authors.affiliation: Johns Hopkins University School of Medicine, 627 Pathology Bld., 6000 North Wolfe Street, Baltimore, MD 21287 USA.
authors.forename: Jorjetta
authors.initials: J
authors.lastname: Ilieva
authors.affiliation: Pediatrics and Developmental Neuroscience, National Institute of Mental Health, Bethesda, MD USA.
authors.forename: Simran
authors.initials: S
authors.lastname: Kalra
authors.affiliation: Pediatrics and Developmental Neuroscience, National Institute of Mental Health, Bethesda, MD USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Swedo
mesh_terms: D001321:Autistic Disorder / Q000276:immunology* / Q000378:metabolism; D018925:Chemokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000134:cerebrospinal fluid; D008137:Longitudinal Studies; D008297:Male; D011446:Prospective Studies
chemical_list: D018925:Chemokines; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins
keywords: Autism; CSF; Chemokine; Cytokine; Growth factor; Immune