Folate Receptor Alpha Autoantibodies Modulate Thyroid Function in Autism Spectrum Disorder

Richard E. Frye, MD, PhD, Jeffrey M Sequeira, MS, Edward Quadros, PhD, Daniel A. Rossignol, MD


The folate receptor alpha (FRα) is essential for folate transportation across the blood-brain barrier and is closely associated with cerebral folate deficiency, a syndrome that commonly presents with autism spectrum disorder (ASD) features. FRα autoantibodies (FRAAs) interrupt FRα function and have a high prevalence in children with ASD. Since the FRα is also located on the thyroid, FRAAs could also interfere with thyroid function. Interestingly, ASD has been inconsistently associated with hypothyroidism. The aim of this study was to determine if thyroid dysfunction in ASD could be related to FRAAs. To this end we investigated the relationship between serum FRAA titers (both blocking and binding) and thyroid stimulating hormone (TSH) in 32 children with ASD. Blocking, but not binding, FRAAs were found to be related to TSH levels. Higher FRAAs were significantly correlated with higher TSH concentrations (r = 0.36, p = 0.025), while ASD children who were positive for blocking FRAAs demonstrated a significantly higher serum concentration of TSH than children who were negative for FRAAs (t(31) = 2.07, p = 0.02). These results are consistent with the notion that blocking FRAAs are associated with reduced thyroid function and suggest that thyroid function should be examined in children with ASD who are positive for the blocking FRAAs. 


Folate receptor autoantibody, autism spectrum disorders, thyroid function, hypothyroidism

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