The etiology and pathogenesis of autism is still unknown. This developmental disease is acknowledged as a syndrome having a broad range of symptoms. It appears that genetics play a major role in the development of this disease. Two lines of evidence support this. First, twin studies have shown concordance rates between 36% to 91% for monozygote twins and 0% to 30% for dizygotic twins, depending on the criteria used to define autism. Second, there is evidence for an association with autism and a region on human chromosomes 6 encompassing the major histocompatibility complex (MHC) that includes HLA class I and class II, and some of the complement components, including C4B. Since concordance rates in monozygotic twins are not 100%, this implies that other factors play a role in the development of autism or are responsible for different subtypes of this disease. Elevated serotonin levels are a consistent finding in autism. Similarly, it appears that the immune response and/or immune regulation in autistic subjects is altered versus control subjects. These immune aberrations often present as a decreased lymphoproliferative response to mitogens and immune reactivity to central nervous system (CNS) proteins. Genetic predisposition (elevated serotonin levels) and/or environmental agents such as viral injections or exposure to toxins in utero or early in life could be responsible for the immune dysregulation. Immune responses against CNS proteins during development could lead to CNS changes that affect behavior and social development later in life. First, we propose to investigate the role of serotonin in inducing dysregulation of the immune response. Second, we examine the specificity and autoreactivity of T cells and antibodies present in children with autism. Third, we plan to determine whether immune effector cells and antibodies induce or mimic CNS features often observed in autistic subjects such as hippocampal and mammillary body changes. Fourth, we propose to perform microarray analyses on RNA isolated from peripheral blood mononuclear cells (PBMC) of autistic children versus control subjects. Determining what genes are altered and identifying their chromosomal positions may lead to additional loci that contribute to this disease.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program--Cooperative Agreements (U19)
Project #
2U19HD035476-06
Application #
6683519
Study Section
Special Emphasis Panel (ZHD1)
Project Start
2002-09-20
Project End
2007-05-31
Budget Start
Budget End
Support Year
6
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Utah
Department
Type
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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