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Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits with restricted interests and repetitive behaviors that currently affect over 2% of children in the US. Autism etiology is a combination of genetic predisposition and exposure to environmental, chemical, and biological insults during gestation and during the first years of life. Particularly, maternal immune dysregulation during pregnancy can act as an insult by changing the fetal-neuro-immune homeostasis and result in neurodevelopmental disorders such as autism in genetically susceptible individuals. Maternal Autoantibody Related Autism (MAR-ASD) is s subtype of autism in which some women develop autoantibodies against proteins necessary for healthy brain development, and during pregnancy, these pathogenic autoantibodies can traverse the developing blood-brain-barrier and cross-react with fetal brain proteins in neuroprogenitor cells, altering neurodevelopment and resulting in altered brain anatomy and impaired behaviors associated with autism in the exposed offspring. In addition, MAR ASD is associated with increased brain volume and more severe behavioral deficits in the affected progeny. This dissertation aims to characterize the maternal autoantibody profiles against 8 critical in fetal brain including CRMP1, CRMP2, GDA, LDHA, LDHB, NSE, STIP1, and YBOX, as well as defining their relationship of these autoantibodies with an ASD diagnosis in their children. Further, the development of an ELISA assay to determine the technical and clinical validity of these autoantibody patterns to be potentially used as ASD-risk biomarkers will also be described herein. Chapter 1 provides an in-depth literature review of maternal-immune dysregulation as an “insult” in the gestational environment that can trigger neurodevelopmental alterations and contribute to the etiology of autism. This chapter focused on epidemiological and experimental data that suggests that ma

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication deficits with restricted interests and repetitive behaviors that currently affect over 2% of children in the US. Autism etiology is a combination of genetic predisposition and exposure to environmental, chemical, and biological insults during gestation and during the first years of life. Particularly, maternal immune dysregulation during pregnancy can act as an insult by changing the fetal-neuro-immune homeostasis and result in neurodevelopmental disorders such as autism in genetically susceptible individuals. Maternal Autoantibody Related Autism (MAR-ASD) is s subtype of autism in which some women develop autoantibodies against proteins necessary for healthy brain development, and during pregnancy, these pathogenic autoantibodies can traverse the developing blood-brain-barrier and cross-react with fetal brain proteins in neuroprogenitor cells, altering neurodevelopment and resulting in altered brain anatomy and impaired behaviors associated with autism in the exposed offspring. In addition, MAR ASD is associated with increased brain volume and more severe behavioral deficits in the affected progeny. This dissertation aims to characterize the maternal autoantibody profiles against 8 critical in fetal brain including CRMP1, CRMP2, GDA, LDHA, LDHB, NSE, STIP1, and YBOX, as well as defining their relationship of these autoantibodies with an ASD diagnosis in their children. Further, the development of an ELISA assay to determine the technical and clinical validity of these autoantibody patterns to be potentially used as ASD-risk biomarkers will also be described herein. Chapter 1 provides an in-depth literature review of maternal-immune dysregulation as an “insult” in the gestational environment that can trigger neurodevelopmental alterations and contribute to the etiology of autism. This chapter focused on epidemiological and experimental data that suggests that ma

This is a report of two patients with subacute cerebellar degeneration associated with cancer whose sera showed antibody activities against nervous tissue elements. Using an immuno-blotting method, the serum of a 68-year-old man with subacute cerebellar degeneration and malignant lymphoma reacted with rat cerebral 250-kd and 110-kd and cerebellar 110-kd acidic cytoplasmic proteins. The serum IgG of the second patient, a 50-year-old woman, who had subacute cerebellar degeneration, Lambert-Eaton myasthenic syndrome and small cell cancer of the lung showed antibody activities to rat cerebral and cerebellar 98-kd neutral cytoplasmic protein and 68-kd membrane protein. These sera did not react with the proteins prepared from human and rat brain obtained several hours after death, which indicated that these antigen proteins were easily degraded and needed to be prepared quickly after death with protease inhibitors. These patients' sera did not react with proteins prepared from rat liver, kidney, spleen, heart muscle and diaphragm and the antigen proteins reacted with these sera might be brain specific. Control sera did not react with any of the brain proteins. The serum of each patients recognized different antigens. Other reported antigens in the literature are also different which indicates those proteins reacting with serum antibody are variable indiviaually among patients with subacute cerebellar degeneration.