Frontiers in Neuroscience (Mar 2016)

Blocking and binding folate receptor alpha autoantibodies identify novel autism spectrum disorder subgroups

  • Richard Eugene Frye,
  • Leanna eDelhey,
  • John eSlattery,
  • Marie eTippett,
  • Rebecca eWynne,
  • Shannon eRose,
  • Stephen Gregory Kahler,
  • Sirish eBennuri,
  • Stepan eMelnyk,
  • Jeffrey M Sequeira,
  • Edward eQuadros

DOI
https://doi.org/10.3389/fnins.2016.00080
Journal volume & issue
Vol. 10

Abstract

Read online

Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). They disrupt the transportation of folate across the blood-brain barrier by binding to the FRα. Children with ASD with FRAAs have been reported to respond well to treatment with a form of folate known as folinic acid, suggesting that they may be an important ASD subgroup to identify and treat. There has been no investigation of whether they manifest unique behavioral and physiological characteristics. Thus, in this study we measured both blocking and binding FRAAs, physiological measurements including indices of redox and methylation metabolism and inflammation as well as serum folate and B12 concentrations and measurements of development and behavior in 94 children with ASD. Children positive for the binding FRAA were found to have higher serum B12 levels as compared to those negative for binding FRAAs while children positive for the blocking FRAA were found to have relatively better redox metabolism and inflammation markers as compared to those negative for blocking FRAAs. In addition, ASD children positive for the blocking FRAA demonstrated better communication on the Vineland Adaptive Behavior Scale, stereotyped behavior on the Aberrant Behavioral Checklist and Mannerisms on the Social Responsiveness Scale. This study suggests that FRAAs are associated with specific physiological and behavioral characteristics in children with ASD and provides support for the notion that these biomarkers may be useful for subgrouping children with ASD, especially with respect to targeted treatments.

Keywords