Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor α autoimmune disorder

Folate receptor α ( FR α) autoantibodies ( FRAA s) are prevalent in autism spectrum disorder ( ASD ). FRAA s disrupt folate transport across the blood‐brain barrier by binding to the FR α. Thyroid dysfunction is frequently found in children with ASD . We measured blocking and binding FRAA s and thyroid‐stimulating hormone ( TSH ), free thyroxine (T4) ( FT 4), total triiodothyronine (T3) ( TT 3), reverse T3 ( rT 3), thyroid‐releasing hormone ( TRH ) and other metabolites in 87 children with ASD , 84 of whom also underwent behaviour and cognition testing and in 42 of whom FRAA s, TSH and FT 4 were measured at two time points. To better understand the significance of the FR α in relation to thyroid development, we examined FR α expression on prenatal and postnatal thyroid. TSH , TT 3 and rT 3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants. FT 4 was rarely outside the normal range. TSH concentration was positively and the FT 4/ TSH , TT 3/ TSH and rT 3/ TSH ratios were inversely related to blocking FRAA titres. On repeated measurements, changes in TSH and FT 4/ TSH ratio were found to correspond to changes in blocking FRAA titres. TSH and the FT 4/ TSH , TT 3/ TSH and rT 3/ TSH ratios were related to irritability on the Aberrant Behavior Checklist and several scales of the Social Responsiveness Scale ( SRS ), whereas TT 3 was associated with SRS subscales and TRH was related to Vineland Adaptive Behavior Scale subscales. The thyroid showed significant FR α expression during the early prenatal period, although expression decreased significantly in later gestation and postnatal thyroid tissue. The results of the present study suggest that thyroid dysfunction in ASD may be related to blocking FRAA . The high expression of FR α in the early foetal thyroid suggests that foetal and neonatal exposure to maternal FRAA s could affect the development of the thyroid and may contribute to the pathology in ASD.