Mounting evidence suggests that some autistic children may be susceptible to an environmental pathogen (most likely a virus or bacterium) resulting from an inherited deficiency of their immune system. Unable to clear the pathogen in a timely and normal fashion, the child would be at increased risk for the pathogen (or pathogenic toxins) to directly interfere with developing brain (or brain function) and/or lead to the generation of an autoimmune mechanism that interferes with brain functioning. Circumstantial evidence for this hypothesis stems from the number of features that autism shares with established immune and autoimmune disorders including: genetic predisposition; general immune imbalances; association with viral and other infections; demonstration of antibodies in the serum against proteins of the central nervous system and an uneven sex distribution. We have recently found additional evidence for the pathogen-autoimmune hypothesis for some cases of autism including an increased frequency of the C4B null allele and elevated representations of the extended haplotype B44-S30-DR4 and two DRbeta1 HVR-3 alleles. All of these genes are part of the major histocompatibility complex that exerts important control over immune function. This component focuses on several recently observed preliminary abnormalities that we have observed in autism which may be related to the WA genes. Findings obtained in this component also will be correlated with results obtained in the other components of this grant including stratification of autism by psychiatric, cognitive, neuroimaging and electroretinographic parameters. Specifically, this component will: perform HLA studies and determine C4 plasma levels on additional autistic and normal subjects; attempt to establish a possible relationship between the HLA system and elevated serotonin levels in autism; explore the basis of possible MHC- associated immunoglobulin IgA deficiency in some autistic subjects; attempt to confirm and expand studies on WA-restricted reactivity with cells of the autistic child by the maternal immune system.

Project Start
2000-06-01
Project End
2001-05-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
4
Fiscal Year
2000
Total Cost
$145,084
Indirect Cost
Name
University of Utah
Department
Type
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Prigge, Molly D; Bigler, Erin D; Fletcher, P Thomas et al. (2013) Longitudinal Heschl's gyrus growth during childhood and adolescence in typical development and autism. Autism Res 6:78-90
Lange, Nicholas; Dubray, Molly B; Lee, Jee Eun et al. (2010) Atypical diffusion tensor hemispheric asymmetry in autism. Autism Res 3:350-8
Chung, Moo K; Adluru, Nagesh; Lee, Jee Eun et al. (2010) Cosine series representation of 3D curves and its application to white matter fiber bundles in diffusion tensor imaging. Stat Interface 3:69-80
Chung, Moo K; Adluru, Nagesh; Lee, Jee Eun et al. (2009) Efficient parametric encoding scheme for white matter fiber bundles. Conf Proc IEEE Eng Med Biol Soc 2009:6644-7
Han, Deok; Singh, Vikas; Lee, Jee Eun et al. (2009) An experimental evaluation of diffusion tensor image segmentation using graph-cuts. Conf Proc IEEE Eng Med Biol Soc 2009:5653-6
Adluru, Nagesh; Hinrichs, Chris; Chung, Moo K et al. (2009) Classification in DTI using shapes of white matter tracts. Conf Proc IEEE Eng Med Biol Soc 2009:2719-22
Glessner, Joseph T; Wang, Kai; Cai, Guiqing et al. (2009) Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature 459:569-73
South, Mikle; Ozonoff, Sally; Suchy, Yana et al. (2008) Intact emotion facilitation for nonsocial stimuli in autism: is amygdala impairment in autism specific for social information? J Int Neuropsychol Soc 14:42-54
Mazefsky, Carla A; Folstein, Susan E; Lainhart, Janet E (2008) Overrepresentation of mood and anxiety disorders in adults with autism and their first-degree relatives: what does it mean? Autism Res 1:193-7
Dominick, Kelli C; Davis, Naomi Ornstein; Lainhart, Janet et al. (2007) Atypical behaviors in children with autism and children with a history of language impairment. Res Dev Disabil 28:145-62

Showing the most recent 10 out of 20 publications