Monday 10 September 2012

Maternal IgG antibodies and offspring autism

Baby, baby @ Wikipedia  
I'm acutely aware that many of the autism and related research papers that I discuss on this blog have the ability to be construed in more than one way.

Take for example the collected data being produced on de novo mutations and older dads as being a risk factor for autism. The message - particularly in the accompanying media - emerging from that body of work suggests that paternal age might well have the ability to affect the risk of offspring developing autism. Indeed a very recent opinion piece in the New York Times (no, not that one on autism and the immune system) reiterates the 'why fathers really matter' point of view.

Hypothetically, if I were an older dad with a child, with a young child with autism, reading such news, perhaps not particularly inclined to think about how risk means risk and not eventuality, I might be taken to ponder my role in my child's presentation of autism in light of this news.

By saying this I'm not making any value judgements on children with autism; accepting that children with autism are children first and foremost just as adults with autism, are adults first. Merely that being faced with such a volume of work and portrayal of such work, could quite easily turn thoughts to 'what if'.

Blame as many, many parents with children with autism already know, has been a particularly cruel theme down the historical timeline of autism as it has in other conditions too (see this piece on parental blame and schizophrenia). I'd like to think that current science and opinion have moved away from the dark times of Bettleheim and co. and refrigerator parenting (well in most places) but realise that generalised connections from research on overweight mums (see here) to systemising dads (see here) and autism for example, and the way they might be portrayed, could also be construed as equalling blame too.

Bear all this in mind as I offer some discussion on this paper by Braunschweig and colleagues* (authors including those from the MIND Institute) who report on the "the effects of a single, low dose gestational exposure of IgG derived from individual MAU [mothers of children with autism] on their offspring's physical and social development". In essence, the authors report that transplanting a purified dose of IgG brain reactive antibodies from mums who have a child with autism into a pregnant mouse model altered the developmental profile and behaviour of offspring mice in a way not totally unlike that seen in cases of autism.

There are a couple of interesting elements related to this work.

  • This is not the first time that maternal antibodies to foetal brain protein have turned up in autism research as per this work on the MET gene which includes just about all the same authorship group. In that case, said antibodies were reported as being more prevalent where maternal mutation in the MET gene was found. 
  • This work sounds pretty similar to that published by Prof. Paul Patterson and colleagues on stimulated immune activation during pregnancy being linked to autistic-like behaviours in offspring, once again in the mouse model. Indeed I also think back to the paper by Goines and colleagues** (discussed here) on the immune profile during pregnancy and offspring autism reporting on a specific cytokine pattern (including interferon gamma) requiring further validation. 
  • Finally, I am drawn back to the whole immune-behaviour link specifically tied back to microglia and autism; accepting that this is not necessarily a direct part of the Braunschweig study per se.

Based on these results, you can perhaps see why I started this post in the cautious way that I did, save any headlines of 'mum's antibodies attack foetus and cause autism' appearing. They don't by the way; given that this was a study conducted on mice - which might be good models for autism but aren't autism - and the reasons for autism coming into being likely to be pretty complex and also quite heterogeneous from individual to individual, phenotype to phenotype. This latest work likely forms a small part of a much bigger picture as per this opinion piece from Dr Judy Van de Water on the SFARI website on the back of the recent NYTimes opinion piece (see here).

Of course science is science, and part of the duty of the whole scientific process is to present any results accurately, dispassionately and without favour. Questions for example about how and why IgG antibodies to brain come about in some mums with children with autism outside of the MET connection really deserve some intensive study as does the issue of specificity (does this only happen in autism?) and the likely complicated gene-environment interactions that might take place.

I'm hoping I've not offended anyone with this or my related posts given the emphasis on research attached to this blog. Blame is absolutely not something intended from my writings; rather illustrating the various directions that autism research is taking and that 'whole-body' approach adopted in quite a few cases. Hopefully also providing a few pointers as to where such research could be a little more focused.


* Braunschweig D. et al. Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model. Journal of Neuroimmunology. August 2012.

** Goines PE. et al. Increased mid-gestational IFN-gamma, IL-4, and IL-5 in women giving birth to a child with autism: a case-control study. Molecular Autism. 2011; 2: 13.

---------- Braunschweig D, Golub MS, Koenig CM, Qi L, Pessah IN, Van de Water J, & Berman RF (2012). Maternal autism-associated IgG antibodies delay development and produce anxiety in a mouse gestational transfer model Journal of Neuroimmunology DOI: 10.1016/j.jneuroim.2012.08.002

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