Biomarker of Children With Familial Autoimmune History
Condition: Autism; Children
MeSH terms: Autistic Disorder
Study type: Observational

Summary: 
      The purpose of this study is to identify biomarkers in this subset of autism patients, design
      a protein based assay system for screening serum for these biomarkers and confirm that these
      serum antibodies are still present at one year's time.
    

Detailed description: 
      Purpose: To identify biomarkers in this subset of autism patients, design a protein based
      assay system for screening serum for these biomarkers and confirm that these serum antibodies
      are still present at one year's time.

      Rationale: Autistic spectrum disorders (ASD), are an increasingly important public health
      concern. Estimates of prevalence of ASDs range from 1/500 to 1/150 children. Retrospective
      data points to immune dysfunction in some of these children and increased frequency of
      familial autoimmune history (FAH) has been reported in children with autism. Behavioral
      responses to immune modulating therapy, though in uncontrolled studies, indicate a role for
      autoimmunity in the pathogenesis. Preliminary prospective work has suggested an immune
      etiology in autism based on the high frequency of brain endothelial antibodies (BEA) in
      children with language regression, 2/3 of whom are on the autistic spectrum and with autism
      without language regression. Follow up studies in a small number of patients showed
      persistence of BEA after at least a year. The specific nervous system epitopes have not been
      identified.

      Population: Approximately 15 children with clinically diagnosed autism who have first degree
      relatives (parents, brothers, sisters, or children) with autoimmune disorders listed on a
      questionnaire. Children on the autism spectrum without autoimmune history and sibling matched
      controls without an ASD from the Simons Foundation Autism Research Initiative (SFARI) with
      deidentified data in the SFARI database will be matched for age, sex and ethnicity. Plasma
      samples and psychometric data from the database will be provided through the database for
      analysis in the laboratory of Dr. Reiter.

      Design: The investigators seek to identify protein biomarkers in the serum of children with
      carefully characterized autism who have a familial autoimmune history in first degree
      relatives (FAH). Cognitive defects in the mouse model of the autism spectrum disorder
      tuberous sclerosis complex can be ameliorated by rapamycin, an immune suppressant drug
      indicating the likelihood that auto-immunity plays a role in autism pathogenesis. To expedite
      the identification of these biomarkers the investigators will use proteomic profiling in
      Drosophila melanogaster. The Drosophila (fly) nervous system is highly homologous to humans
      at the molecular level and genetic pathways for synaptic development and function are highly
      conserved. Several human neurogenetic diseases including Huntington, Alzheimer, fragile X,
      spinal cerebellar ataxia and Parkinson disease have been successfully studied using fly
      genetic models. Monoclonal antibodies generated against total fly brain homogenate cross
      react with human neuronal tissue and are highly specific for the recognition of particular
      subsets of neurons in the human nervous system. Our goal is to identify biomarkers in this
      group of autism patients, design a protein based assay system for screening serum for these
      biomarkers and confirm that these serum antibodies are persistent. A similar approach was
      taken by Dr. Levin to identify the central nervous system (CNS) autoantigen in the human
      T-lymphotropic virus type 1 disease associated myelopathy/tropical spastic. Dr. Reiter's
      group currently uses proteomic profiling in Drosophila to identify the protein targets of the
      Angelman syndrome gene, UBE3A.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Children with or without autism
      
Biospecimen description: 
      Blood
    
Keywords: autism; children