Monday, 11 July 2016

Expanding MAR autism

MAR autism - maternal autoantibody-related autism - is a term that has graced this blog before (see here). Describing a state where autoantibodies directed against foetal brain proteins have been detected in some mothers who have children diagnosed with an autism spectrum disorder (ASD), the suggestion is that such evidence further substantiates a role for various maternal immune functions and processes when it comes to offspring risk of at least some types of autism.

Although interesting, the research road travelled by MAR autism has not been a smooth one (see here). Indeed one of the outstanding questions has been whether the detection of such autoantibodies is more or less likely when various other conditions affecting the mother might be present (see here) and perhaps synergistically elevating the risk of offspring autism. The paper by Paula Krakowiak and colleagues [1] further explored this question and concluded that: "mothers whose children had severe ASD and who experienced diabetes were more likely to have anti-fetal brain autoantibodies 2–5 years later."

Some media about the Krakowiak study can be seen here. Based on participants - "227 mothers of 2–5 year old children with confirmed ASD" - all enrolled in CHARGE (be in CHARGE!) researchers set about looking at whether "ASD-specific maternal autoantibodies identified postnatally were associated with metabolic conditions (MCs) during gestation." Said metabolic conditions (MCs) included "diabetes, hypertensive disorders, and prepregnancy obesity or overweight, ascertained from medical records or structured telephone interviews." Indeed Paula Krakowiak has some research history with MCs in mind (see here) that has subsequently been replicated in other cohorts (see here).

Results: well, aside from a quarter of mothers presenting with those autoantibodies (based on the analysis of archived blood samples) authors reported that: "Ab+ [anti-fetal brain autoantibodies positive] prevalence was higher among mothers with diabetes, hypertensive disorders, or overweight compared to healthy mothers, but differences were not statistically significant." What this means is that overall there was a trend towards elevated risk of Ab+ in  those mothers with various metabolic conditions but this might have just been a chance finding. Unfortunately some of the media reports on this specific point are found wanting...

When it came however to looking at those mothers who had children who "exhibited severe ASD" they suggested that those diagnosed with type-2 diabetes or gestational diabetes "were 2.7-fold more likely to be Ab+." Further: "Gestational diabetes specifically was associated with a 3.2-fold increased Ab+ prevalence."

As per some of the media interest in these results there are a few [cautious] 'take-away messages' from the findings. The idea for example, that the presence of certain metabolic conditions "may alter the maternal immune tolerance to the fetus during pregnancy" is an important one in the context of words like 'inflammation' being potentially involved (see here for another example of this). I would however like to see a little more science done on the specific biology of how obesity might bring about autoantibodies with autism specifically in mind based on other findings [2].

That preferential screening of the offspring of those mothers diagnosed with a metabolic condition either before or during pregnancy might be offered is another message bearing in mind how stretched screening and diagnostic services seem to be in many parts of the world. The idea also that where and when 'severe ASD' is reported, further research investigations might focus in further on this topic and how findings might manifest in the children with ASD themselves is also deserving of attention.

Oh, and then there is the further evidence afforded to the term 'the autisms' by the Krakowiak results...


[1] Krakowiak P. et al. Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. Autism Research. 2016. June 17.

[2] Arai S. et al. Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells. Cell Rep. 2013 Apr 25;3(4):1187-98.

---------- Krakowiak P, Walker CK, Tancredi D, Hertz-Picciotto I, & Van de Water J (2016). Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions. Autism research : official journal of the International Society for Autism Research PMID: 27312731