Behavioral correlates of maternal antibody status among children with autism

Abstract

Autism spectrum disorders (ASDs) affect approximately 1 in 110 children in the United States. This report profiles fetal-brain reactive autoantibodies of a large cohort of mothers of children with autism and controls, yielding significant associations between the presence of IgG reactivity to fetal brain proteins at 37 and 73 kDa and a childhood diagnosis of full autism (p = 0.0005), which also correlated with lower expressive language scores (p = 0.005). Additionally, we report on reactivity to proteins at 39 and 73 kDa, which correlated with the broader diagnosis of ASD (p = 0.0007) and increased irritability on the Aberrant Behavioral Checklist (p = 0.05). This study provides evidence of multiple patterns of reactivity to fetal brain proteins by maternal antibodies associated with ASD and specific childhood behavioral outcomes.

Fig. 1

Representative western blot of maternal antibody reactivity to 37, 39 or 73 kDa antigens and non-reactive control. Reactivity of plasma IgG from two AU mothers one TD and one DD mother to fetal human (H) and fetal Rhesus macaque brain proteins of 152 day, 109 day and 49 day gestation are shown. Arrows indicate 37, 39 and 73 kDa bands. Among the Rhesus brains tested, antigen expression appears highest in late gestation (152 day sample)

Fig. 2

Serial dilution of maternal plasma samples. Representative maternal antibody samples shown react at 37 and 73 or 39 and 73 kDa were diluted at 1:400, 1:800, 1:1,600 and 1:3,200 and were used to probe a western blot of 152 day gestation fetal Rhesus brain protein. Reactivity was observed at 1:1,600 dilution for all antigens

Fig. 3

Maternal antibody reactivity to fetal and adult proteins. a Maternal antibody reactivity to the 37/73 kDa (arrows, left strips) and the 39/73 kDa (arrows, right strips) antigens in human fetal brain (hFB) and Rhesus macaque fetal brain (rFB) was highly consistent. Reactivity to the 37 kDa antigen was found in human adult brain (AB), human fetal tissues including brain (hFB), fetal cerebellum (FC), fetal frontal lobe (FFL), fetal brain stem (FBS) and fetal small intestine (FSI) as well as rhesus fetal brain (rFB). Reactivity to the 73 kDa antigen was faintly detectible in AB and was present in all fetal CNS-derived protein sources but not in SI. Reactivity to the 39 kDa antigen was observed in AB, hFB, FL and rFB but not in FC, FBS or FSI, suggesting a regional CNS expression of this antigen