Previous studies have been suggested the role of maternal autoantibodies on the development of autism. To further these studies, a research has been done by the University of California at Davis to examine the influence of maternal antibodies on human fetal and adult brain proteins. The subjects comprised of 61 mothers of children with autism (AU) and 102 mothers of children without autism (non-AU) as a control group. Western blot was used to compare the reaction of antibodies (proteins) from AU mothers and from (non-AU) mothers against fetal and adult brain proteins.
The analysis from western blot showed reactivity of antibodies of (AU) mothers, which was presence as two protein bands approximately at 37kD and73kD, against fetal brain but not adult brain. The control group, (non- AU) mothers’ antibodies, showed no reaction against fetal brain. When the result was compared from (AU) mothers with (non-AU) mothers, more than a quarter of AU mother’s protein (antibodies) bands were different than the control group. The reason why all (AU) mothers’ antibodies did not show bands is due to heterogeneity of autism.
Since maternal IgG is the only antibody that can be transferred from mother to child via placenta, it can be detected in the fetal circulation after 18 weeks of gestation. Immunoblot from fetal brain has shown the heavy and light bands of IgG, which supports the notion that maternal IgG is transported to fetal brain during gestation. The gestation period is a critical time for fetal early neurodevelopment therefore; the transport of maternal IgG to fetal brain interferes with this period. Despite benefits that majority of maternal IgG offer to fetal, some pathogenic maternal IgG are responsible for autoimmune diseases like lupus syndrome, abnormal thyroid function and etc.
The data from this study provides evidence that there is an association between biomarkers present in maternal immune system and diagnosis of autism. “The presence of specific anit-fetal brain antibodies in the plasma of mothers during pregnancy may be a potential trigger that, when paired with genetic susceptibility, is sufficient to induce a downstream effect on neurodevelopment leading to autism.” Although other studies have shown similar findings as this study, however further research is needed to identify the protein targets of these maternal antibodies, which will help us in understand the mechanisms in interaction of proteins and maternal antibodies.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2305723/
It seems odd that otherwise healthy, control-matched mothers would be creating antibody against fetal brain proteins. Since the article didn't provide any information on the parents other than maternal age, it is difficult to tease out what else might be at work in this experiment. I am curious what the prevalence of Rh-discrepancies were in these groups, as well as how the maternal histories of allergy or other humorally-mediated immune responses compared in these two groups.
ReplyDeleteWhile this is a very interesting find, the study didn't go far enough. When studying mother-child interactions in-utero, it's not enough to get diagnostic info on the child but only incomplete medical history of the mothers. In this study they did administer a questionnaire re: family history of autoimmunity, but didn't refer to is. I suppose we can assume it was inconclusive, but what about the moms themselves?
It seems likely to me that these mothers may be more prone to IgG cross-reactivity either from previous infectious disease (think anti-strepIgG and RHD) or allergy, although the latter seems less likely. This study should have gone farther in its reporting of maternal health history and mother vs child immunity, but it's an interesting place to start. Good find!