Studies of a Possible Autoimmune Etiology of Autism

My presentation summarizes the results of collaborative studies between our laboratory and the laboratory of Dr. Judy Van de Water at the M.I.N.D. Institute and Center for Children's Environmental Health at UC Davis. Initial studies by Dr. Van de Water and colleagues were designed to characterize potential immunological dysfunction in children with autism. Among the many abnormalities that have been discovered for at least some children with autism are indications of abnormal autoimmune responses. Van de Water and her students found that approximately 20% of children with autism demonstrate abnormal autoantibodies directed at mature brain tissue. Work carried out by Dr. Sharifia Wills in our laboratory has determined that at least some of these abnormal antibodies identify classes of GABAergic neurons in the cerebellum and other brain regions. I will present evidence indicating the types of staining produced by these antibodies in tissue throughout several brain regions from macaque monkeys. Van de Water and colleagues have also identified autoantibodies in about 12% of women who have had children with autism that are directed at fetal brain tissue. This raised the possibility that at least one cause of autism may be the transplacental transfer of these antibodies to the fetal brain leading to brain damage and the onset of autistic symptoms. Dr. Lorne Martin, a postdoctoral fellow in our laboratory, in collaboration with members of the Van de Water laboratory, conducted a study in which these antibodies were purified and injected into pregnant rhesus monkeys. The behavior of the offspring of these animals was then studied from birth for approximately 1 1/2 years. A striking observation about the animals that received the autism IgG but not IgG from mothers of typically developing children is that they developed profound stereotypies across many behavioral settings and evaluations. I will discuss these studies related to a maternal autoimmune etiology of autism and their implications for the detection of one class of risk factors and briefly describe our ongoing replication studies.