Psychiatry

Maternal Antibodies May Trigger up to 25% of Autism Cases

Judy Van de Water, PhD, and colleagues have coined the term "maternal autoantibody–related," or MAR, autism

Maternal antibodies that interfere with fetal brain proteins during pregnancy may be responsible for roughly one quarter of cases of autism spectrum disorder (ASD), a new study suggests.

Critical Role in Brain Development
The antigens include the following: lactate dehydrogenase A and B (LDH), cypin, stress-induced phosphoprotein 1 (STIP1), collapsin response mediator proteins 1 and 2 (CRMP1, CRMP2), and Y-box-binding protein.
In 246 mothers of children with ASD and 149 mothers of typically developing children, maternal reactivity to any of these antigens, individually or in combination, was statistically significantly associated with having a child with ASD (odds ratio, 3.26; 95% confidence interval, 1.92 - 5.53), the researchers found.
Exclusive reactivity to specific antigen combinations was noted in 23% of mothers of children with ASD and in only 1% of mothers of typically developing children.
Behaviorally, the researchers found that children with ASD whose mothers have autoantibodies targeting a subset of these antigens had greater overall impairment compared with children with ASD whose mothers lack these particular antibodies.
This study, coupled with several prior studies, provides "compelling evidence" that placental transfer of maternal antibodies could alter fetal neurodevelopment and could play a role in autism, they note.
"Each of the target autoantigens...is known to have a critical role in the developing brain and interference with the level or function of more than one of them could act synergistically to change the trajectory of brain development," the investigators write.
"The effect of MAR autoantibodies could occur through a direct antigen–antibody interaction, thereby either decreasing the abundance of or causing functional interference of the target proteins. Alternatively, the presence of these maternal antibodies may merely serve as a biomarker of cell destruction," they point out.
Clinical Implications
Dr. Van de Water told Medscape Medical News that their new findings have potential implications for diagnosis and treatment.
"We can work toward the development of a clinical test to determine the risk of having a child with autism preconception or during the early postnatal period, which would be especially important in the high-risk population of those women who already have at least 1 child on the spectrum," she said.
"It's important to note that this would be a rule-in test, as a negative result would not necessarily mean that you would have a typically developing child, but if you are positive, your risk of having a child with ASD is greater than 99%," she added.
"The second implication is that we can explore a target therapeutic approach in the future through a better understanding of the specific antibody targets," Dr. Van de Water said.
She said her group is now working on identifying the specific sites on the protein targets that are recognized by the MAR antibodies (the epitopes), "which will allow us to build a more specific animal model. We will use this model to determine the mechanism through which these antibodies affect neurodevelopment, or their true pathologic significance."

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Medscape Medical News by M.Madan Mohan. Librarian, VMMC.