Several recent immunogenetic and clinical findings suggest a pathogenic relationship between autism and faulty immune regulation. The long-term objective of this project is an attempt to provide compelling evidence for or against the idea that unregulated immune processes create a specific brain lesion resulting in autism. The immediate objectives are to search for evidence that faulty maternal-fetal immune regulation is associated with autism and that such impaired regulation allows maternal immune elements to exist which have the potential to create brain lesions. An additional current objective is to determine the mechanistic basis of abnormal immune function of children with autism.
The specific aims are: 1. study sharing of genetically-determined human leukocyte antigens (HLA) and extended haplotypes by parents of autistic children and attempt to determine if any HLA antigen or extended haplotype is associated with autism; 2. investigate the bases of abnormal T-cell function in mothers of autistic children using the T-cell blastogenesis assay, the interleukin assays and lymphocyte enumeration; 3. search for a lack of blocking factors in the sera of mothers of autistic children using the mixed lymphocyte culture assay; 4. explore maternal immunity against lymphocyte antigens of the autistic child, father and other children in the family using the antibody-dependent cell-mediated cytotoxicity assay and the complement-dependent cytotoxicity assay; 5. study the ability of OKT4+ suppressor T- cells in patients with autism to block antibody production by maternal lymphocytes, and 6. extend studies on abnormal T-cell immunity and natural killer cell activity in autistic patients.
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