Date of Award:

5-1-1998

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Biology

Committee Chair(s)

Daryll B. DeWald

Committee

Daryll B. DeWald

Committee

J. Dennis Odell

Committee

Gregory J. Podgorski

Abstract

The exact pathogenesis of autism is not known, but experimental evidence shows that there are genetic, immunologic, and even microbial factors involved in its development. A potential genetic and immunologic link to the development of autism is the presence of the HLA-DRβ1*0101 and *0401 genes in autistic children or their mothers. These genes have been found 5 to 6 times more often in autistic children or their mothers than in normal subjects. It has also been shown that people expressing these genes might be tolerant to self-peptides from the third hypervariable region of the HLA-DRβ1 protein. The third hypervariable region of HLA-DRβ1*0401 has sequence identity to immunogenic proteins from known human pathogens such as the Epstein-Barr virus and Escherichia coli. It has therefore been hypothesized that tolerance to proteins from pathogenic microorgansims plays a role in autism by allowing a pathogen to persist and damage the central nervous system resulting in the autistic disorder. The data in this study do not support this hypothesis; however, they provide compelling evidence that there are significant differences in responses to HLA-DRβ1 HVR-3 peptides by peripheral blood lymphocytes of autistic children and their mothers as compared to normal children and their mothers. The comparisons in this study consistently showed that stimulation index values for the cells of autistic children and their mothers were higher than stimulation index values from the cells of normal children and their mothers. This overstimulation of lymphocytes would indicate that the cells of autistic children and their mothers have deficiencies in regulation which could lead to an autoimmune reaction. If the autoimmune reaction targeted a protein of the central nervous system, damage could occur that could result in the development of autism. Further studies in this area are warranted to identify the link between increased lymphocyte responses to peptides from the third hypervariable region of HLA-DRβ1 and the development of autism.

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