Genetics of Childhood Disorders: XXXV. Autoimmune Disorders, Part 8: Animal Models for Noninflammatory Autoimmune Disorders of the Brain

Abstract

Useful animal models for the investigation of autoimmune disorders that involve the brain are essential, especially in children in whom access to the CNS is limited. The paucity of such models can hinder an understanding of causation, pathogenic mechanisms, and treatments. This is particularly true when one is investigating postulated antibody-mediated disorders in which evidence supporting pathogenesis is derived from in vitro studies. The interpretation of such studies is confounded by the frequent nonpathogenic antineuronal antibody binding associated with chronic disorders, such as autism, type 1 diabetes mellitus, as well as normal aging. Differentiating pathogenic from nonpathogenic antibodies cannot be done without a biological assay such as an animal model. This need is seen in the ongoing discussion of the pathogenesis of autoantibodies in childhood Tourette syndrome (TS), obsessivecompulsive disorder (OCD), pediatric autoimmune neuropsychiatric disorders associated with streptococcus (PANDAS), and Sydenham chorea (SC). An animal model should reflect the type of immune response occurring or postulated to occur in the brain, utilize brain regions involved in the disorder, and maintain the brain’s unique immune environment. When studying putative immune brain disorders, it is useful to initially group disorders by the presence or absence of acute inflammation. This distinction is important because