Mother’s antibody attack linked to autism

"Now we not only have a marker, but we are starting to understand the actual mechanisms of what causes autism. 

These findings can greatly enhance our understanding of the origins of some cases of autism and may directly lead to screening tests and treatments to prevent it," says Daniel B. Campbell, one of the study's principal investigators.

The research is the first to demonstrate a genetic mechanism at play in the development of autism, raising the possibility of a genetic test for women at risk, according to the study published online in the journal Translational Psychiatry.

“Our study gives strong support for the idea that, in at least some cases, autism results from maternal immunity gone overboard,” says Judy Van de Water, professor of internal medicine at the University of California, Davis, who is affiliated with the MIND Institute.

“This is the first time that a genetic factor known to be important in autism and its effects have been demonstrated.”

For the study, Van de Water and colleagues examined the action of the MET gene, which has a known association with autism, among 200 mothers of children with autism and 150 mothers of typically developing children enrolled in the Northern California-based Childhood Autism Risks from Genetics and the Environment (CHARGE) Study.

All of the study participants were between 2 and 5 years of age at the time of study enrollment, lived with one biological parent, and spoke either English or Spanish.

The researchers found that the C-allele of the MET gene is more common in mothers with several immunologic abnormalities that might contribute to the development of autism.  Analysis of the MET C-allele is a method of determining susceptibility for immune dysregulation in the mothers.

One abnormality they attributed to the MET C-allele is the presence of antibodies against fetal brain proteins in the blood of the mothers.

These brain-attacking antibodies occur in some mothers with an autistic child, but are not found in mothers of typically developing children.

It is believed that these antibodies somehow injure the developing brain of the fetus, and in some instances may cause autism.

Researchers do not yet know when or how the antibodies are formed, or precisely what happens to the brain tissue exposed to them, but based on a collaborative paper with Loren Martin at Azuza Pacific University, they appear to have pathologic significance, or a functional effect on brain development, changing the way the brain develops.

Van de Water and her group are still working on the precise effect of these maternal antibodies on the developing brain.

MET protein levels were also found to be reduced in cells from mothers with one C-allele and one normal allele, and were even lower in those with two C-alleles. Lower MET protein on the cell surface may increase susceptibility to a more intense and prolonged immune response when the cells are activated, like exposure to a bacteria or virus.

This, in turn, could make these individuals more prone to forming antibodies against “self” proteins, such as those found in the fetal brain.