Characterization of Maternal Plasma Antibodies to Fetal Brain in Autism

Background: There is mounting evidence of an association between the presence maternal anti-fetal brain autoantibodies and development of autism in some children. Particularly, human fetal brain antigens of approximately 37kD and 73kD are detected by western blot in some mothers of children with autism. Observations suggest that the antigen(s) are relatively highly expressed in human as well as Rhesus macaque fetal brain. Characterization of the antigen distribution during fetal development, as well as in several mammalian cell lines of different origin, will help in identifying the target(s) of, and a potential role for, these antibodies.

Objectives: Determine the temporal distribution and abundance of the autoantigen(s) in fetal Rhesus monkey brain at several developmental time points. To help determine which cell types express the autoantigen(s), several mammalian cell lines were also assessed.

Methods: Plasma IgG antibodies from mothers of children with autism as well as mothers of typically developing children as matched controls. Samples from each group were used to stain western blots of fetal Rhesus macaque brain ranging from 49 to 152 days gestation. Protein extracts of neuronal and non-neuronal cell lines were similarly assessed for antigen expression by western blot.

Results: Expression of the specific fetal brain antigens recognized by maternal antibodies was present at low levels in early gestation (day 49) and peaked at 152 days. Furthermore, expression of these antigens was observed in two transformed neuronal cell lines, but absent in a fibroblast and breast cancer cell line.

Conclusions: We have demonstrated that the specific proteins recognized by maternal IgG from mothers of children with autism are expressed more abundantly later in fetal brain development. This suggests that the antigens recognized by these maternal antibodies may relate to higher order function due to their later temporal expression.  The presence of the autoantigen in some cell lines will provide information as to the tissue specificity as well as an additional source of antigen for protein identification.