Project 2: Immunological Susceptibility of Autism

University Of California At Davis, Davis CA

Investigators

Linked publications & trials

Abstract

Recent studies indicate that immune function in children with autism spectrum disorder (ASD) is[unreadable] profoundly altered compared to developmentally healthy controls. There is a strong interface between the[unreadable] immune system and the neurologic network, and successful neurodevelopment is contingent upon a[unreadable] successful interaction between these two systems. We have identified several aspects of immune[unreadable] dysfunction in patients with autism compared with typically developing controls. These include a reduced[unreadable] response to vaccine antigens of bacterial origin, altered cytokine levels in plasma and upon stimulation of[unreadable] PBMC, increased levels of leptin in patients with early onset autism, and autoantibodies to brain antigens.[unreadable] This wide and complex variety of immune anomalies noted in our first funding period is in keeping with the[unreadable] broad range of phenotypes encompassed by the autism spectrum. Thus, we will build upon our earlier[unreadable] findings of both serologic and cellular changes in immune function. While our studies in the previous project[unreadable] period were aimed at a broad analysis of immune function in patients with autism, the current proposal will[unreadable] address the mechanisms responsible for the numerous alterations in immune homeostasis uncovered in our[unreadable] earlier studies. Therefore, our primary focus will be on the mechanisms responsible for such anomalies in[unreadable] immune function through an in depth analysis of cellular immune function. Our overall hypothesis is that[unreadable] patients with autism have a fundamental defect at the cellular level that ultimately leads to[unreadable] abnormalities in immune function and heightened susceptibility to environmental triggers. To[unreadable] examine this, we propose to: (1) examine longitudinally the serologic profile of children with ASD to ascertain[unreadable] whether the various immune changes noted in our first studies are maintained and/or deteriorating further;[unreadable] (2) determine which immune cell population(s) plays a critical role in the immune dysfunction seen in patients[unreadable] with autism; and (3) fully characterize the autoantibody response in a subpopulation of children with ASD[unreadable] and some mothers of children with ASD. It must be noted that due to the highly heterogeneous nature of[unreadable] autism, there will potentially be immunologic differences that relate to sub-groups of patients with autism.[unreadable] Therefore, we will carefully define the study groups based on our current data to include children with early[unreadable] onset autism, children with delayed onset/regressive autism, general population controls, and children with[unreadable] developmental disorders without ASD. The studies will be performed on CHARGE subjects formerly[unreadable] analyzed by our laboratory (CHARGE-BACK study). This will allow us to extend our prior studies[unreadable] longitudinally to determine if the immune dysregulation, such as increased leptin levels in the early onset[unreadable] patients, remains over time. The following aims address both the serologic and cellular aspects of immune[unreadable] function in patients with autism.