Grantee Research Project Results

2005 Progress Report: Environmental Factors in the Etiology of Autism; Cell Activation/Signaling Core

EPA Grant Number: R829388C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R829388
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: UC Davis Center for Children's Environmental Health and Disease Prevention
Center Director: Van de Water, Judith
Title: Environmental Factors in the Etiology of Autism; Cell Activation/Signaling Core
Investigators: Van de Water, Judith , Ashwood, Paul
Institution: University of California - Davis
EPA Project Officer: Aja, Hayley
Project Period: September 30, 2001 through September 29, 2002
Project Period Covered by this Report: September 30, 2004 through September 29, 2005
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health

Objective:

To determine if children with autism possess abnormal humoral and acquired immunity and abnormal responses to xenobiotic triggers.

Progress Summary:

In this funding period, several seminal findings regarding altered immunological markers that distinguish autistic children were documented.

Plasma leptin levels distinguish autism phenotypes. Children with autism have significantly higher plasma leptin levels compared with typically developing controls (Ashwood et al. 2005). When the subjects with autism were further classified into the clinical phenotypes of regression or early onset autism, there were highly significant differences between patients with early onset and all groups including patients with regression (p<0.026), typically developing controls (p<0.0024), and developmentally delayed controls (p<0.007). This finding is significant because leptin represents the first biologic marker that could potentially differentiate between two clinical phenotypes of autism and provides evidence of a biologic distinction between those children with early onset disease and those who develop and then lose language and social skills. Considering the role of leptin in autoimmunity and regulation of the nervous system it may be a relevant biomarker of susceptibility to environmental triggers.

Children with autism have significantly depressed levels of immunoglobulins. Analysis of immunoglobulin levels in autistic children indicates significant depression in plasma concentrations of IgG, IgM and IgA compared to those found in age and gender matched children from the general population (p<0.004).

Children with autism have significantly depressed responses to bacterial vaccine antigens. Recall responses to Diptheria, tetanus toxoid, and Bordetella pertussis antigens were tested by measuring IgG levels subsequent to in vitro challenge. Autistic children displayed significantly depressed responses to all three antigens, with the most depressed response to Bordetella. The response of the siblings to all three antigens was similar to that of their typically developing group. By contrast, recall responses to viral vaccine antigens was not different between patients and controls when time-out from vaccination was taken into account.

Children with autism possess a distinct cytokine profile. Autistic children had significantly increased levels of pro-inflammatory cytokines IL-6 and IL-12 compared to general population and developmental delay controls.

Mothers of children with autism and autistic children possess serum autoantibodies that recognize brain proteins. Positive staining in several brain regions is more frequently seen with IgG isolated from autistic children compared to their siblings, or the developmentally delayed group. Specifically, antibodies in the plasma from autistic patients show strong cytoplasmic immunostaining of what appear to be Golgi type II cell in the Purkinje layer of Rhesus monkey cerebellum, in comparison with staining using plasma from age-matched controls.

Journal Articles on this Report : 3 Displayed | Download in RIS Format

Publications Views
Other subproject views:	All 5 publications	3 publications in selected types	All 3 journal articles
Other center views:	All 179 publications	162 publications in selected types	All 161 journal articles

Publications
Type	Citation	Sub Project	Document Sources
Journal Article	Ashwood P, Van de Water J. A review of autism and the immune response. Clinical & Developmental Immunology 2004;11(2):165-174.	R829388 (Final) R829388C002 (2005)	Full-text from PubMed Abstract from PubMed Full-text: Clinical and Developmental Immunology-Full Text PDF Exit
Journal Article	Ashwood P, Van de Water J. Is autism an autoimmune disease? Autoimmunity Reviews 2004;3(7-8):557-562.	R829388 (2006) R829388 (Final) R829388C002 (2005)	Abstract from PubMed Full-text: SemanticsScholar-Full Text PDF Exit Abstract: Science Direct-Abstract Exit
Journal Article	Lawler CP, Croen LA, Grether JK, Van de Water J. Identifying environmental contributions to autism: provocative clues and false leads. Mental Retardation & Developmental Disabilities Research Reviews 2004;10(4):292-302.	R829388 (2006) R829388 (Final) R829388C002 (2005)	Abstract from PubMed Abstract: Wiley Online Library-Abstract Exit

Supplemental Keywords:

Autism, immunotoxicity, autoimmunity, mercury, PCBS, PBDEs,, RFA, Health, Scientific Discipline, PHYSICAL ASPECTS, ENVIRONMENTAL MANAGEMENT, Health Risk Assessment, Chemistry, Risk Assessments, Susceptibility/Sensitive Population/Genetic Susceptibility, Disease & Cumulative Effects, Physical Processes, Children's Health, genetic susceptability, Biology, Risk Assessment, chemical exposure, neurotoxic, xenobiotics, biomarkers, epidemiology, gene-environment interaction, neurodevelopment, pesticides, exposure, halogenated aromatics, children, neurobehavioral, neurodevelopmental, neurotoxicity, etiology, susceptibility, human exposure, neurobehavioral effects, autism, biological markers, mechanisms, exposure assessment, neurological development, biomarker, synergistic interactions

Progress and Final Reports:

Original Abstract

Final

Main Center Abstract and Reports:

R829388 UC Davis Center for Children's Environmental Health and Disease Prevention

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829388C001 Environmental Factors in the Etiology of Autism; Analytic Biomakers (xenobiotic) Core
R829388C002 Environmental Factors in the Etiology of Autism; Cell Activation/Signaling Core
R829388C003 Environmental Factors in the Etiology of Autism; Molecular Biomakers Core
R829388C004 Environmental Factors in the Etiology of Autism; Childhood Autism Risks from Genetics and the Environment (The CHARGE Study)
R829388C005 Environmental Factors in the Etiology of Autism; Animal Models of Autism
R829388C006 Environmental Factors in the Etiology of Autism; Molecular and Cellular Mechanisms of Autism

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.