Biomarker of Children With Familial Autoimmune History

Biomarker Discovery In Children With Autism Plus Familial Autoimmune History

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.

Study Overview

• Status: Completed
• Conditions: Children; Autism

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.

• Study Type: Observational
• Enrollment (Actual): 58

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38103
      • LeBonheur Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 17 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children with or without autism

Description

Inclusion Criteria:

• 4-17 years of age
• male or female
• autistic subjects must have a diagnosis of autism spectrum disorder

Exclusion Criteria:

• Controls must have no diagnosis of autism spectrum disorder.
• controls must be typically developing children without behavioral deviations.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Autism with FAH; Children diagnosed with autism with first degree relatives that have autoimmune disorders.
Autism without FAH; Children diagnosed with autism without first degree relatives that have autoimmune disorders.
Control; Typically developing children

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of autistic participants with autoimmune markers	The designed techniques will be used to first identify and then determine the frequency of autoimmune markers cross reacting with fly neuronal proteins in children with carefully characterized autism with and without a positive familial autoimmune history (FAH) in a first degree relative compared to typically developing children without FAH.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of neuronal protein autoimmunity	Presence of autoantibodies will be correlated with presence of a positive FAH in a first degree relative. Identification of neuronal protein autoimmunity will allow further investigation of etiological factors and possible immune modulating treatment in children with autism.	5 years

Collaborators and Investigators

• Sponsor: Le Bonheur Children's Hospital
• Collaborators: University of Tennessee Health Science Center
• Investigators: Principal Investigator: Kathryn A McVicar, MD, LeBonheur Children's Medical Center; Principal Investigator: Larry T Reiter, PhD, LeBonheur Children's Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (ACTUAL): May 1, 2016
• Study Completion (ACTUAL): August 1, 2016

Study Registration Dates

• First Submitted: February 23, 2012
• First Submitted That Met QC Criteria: February 28, 2012
• First Posted (ESTIMATE): February 29, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): August 19, 2016
• Last Update Submitted That Met QC Criteria: August 17, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: children; autism
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Autistic Disorder
• Other Study ID Numbers: 08-00206-XP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED