Thursday, 5 April 2012

Gender, autoimmunity and autism

With all the challenges facing autism research in terms of the heterogeneity of the condition, the increased likelihood of certain comorbidity and the lack of objective markers (despite some good efforts), a touch of blue-sky thinking is often required. So for example, appreciating that there may be subgroups of people diagnosed with an autism spectrum condition who present with common issues as per the up-coming area of endophenotypes or looking at possible commonalities outside of the immediate parameters of the condition for potential clues about the condition, bearing in mind the correlation-is-not-causation motif.

With such sentiments in mind I'd like to talk about some speculative but interesting thoughts from this paper by Kevin Becker* on the male gender bias in autism and pediatric autoimmunity. I have had some contact with Dr Becker about this and his other papers** and he is interested to see what opinions there are about some of the ideas he is expounding. Viewers, after reading this, please do opine.

Before progressing through the paper, Dr Becker has quite a publication record in autism and other areas as evidenced by papers such as this one on autism, asthma, immunity and the hygiene hypothesis (full-text) and this one on autism, asthma and paracetamol (acetaminophen) use (full-text), both of which approach areas near to my research heart. This paper (full-text) on the tight junction protein, claudin 7 also caught my eye in view of my interest in the extra-intestinal effects of gut permeability (see here) as did this paper (full-text) on that most lovable tryptophan hydroxylase. Do I even need to mention reference to the science of epigenetics (full-text) or are you getting bored of that already?

Enough of the appreciation society comments and onwards to the current paper:

  • As per previous mentions, the often quite startling gender differences skewed towards males is one of the more defining characteristic of autism spectrum conditions (not including Rett syndrome). One could therefore suggest that this sex ratio difference might be a good place to start in research terms for quite a few people on the autism spectrum.
  • Autoimmunity has also had more than a passing interest in relation to some cases of autism (remember this post) and in particular the coincidence of various autoimmune conditions in cases of autism - and their families - such as diabetes (type 1) for example. 
  • Becker hypothesises on some connection between the male bias in both presentation of autism and pediatric autoimmune conditions and the possibility of some shared aetiological features. His evidence is multi-fold but includes: (a) autoimmune conditions normally come in packs as per the suggestion on the recent psoriasis post remembering the possibility of a relationship between autoimmunity and autism, (b) you may well be saying to yourself that autoimmune conditions in general tend to favour females rather than males so how could there be a connection? Well you'd be half right because adult presentation is often more frequent in females. The same however does not necessarily apply to pediatric presentation where roles seem to be reversed and males are perhaps the more fragile gender. Becker presents quite a bit of data to support a variable male skewing of rates of some autoimmune conditions in pediatric cohorts, (c) hormones inevitably get a mention and the testosterone-autism link including the recent RORA findings, (d) remembering the chromosomal makeup of males compared to females, the X chromosome also comes into view and various research on how issues with the X chromosome might similarly impact on both autism and various autoimmune conditions.

There are some interesting ideas in the paper which make a lot of sense. The focus on hormonal issues during pregnancy affecting subsequent offspring function is a trendy area for autism research at the moment and follows quite a few other papers in looking at this sensitive period such as the vits & SNPs research publication.

Having said that the suggestions are still speculative and perhaps require further study in a real-world setting. So, things like comparisons between male and female children both with and without autism (and/or learning disability, speech & language disorder, even the BAP) in terms of autoimmune comorbidity, more detailed inspection of some of the underlying genetic findings overlapping between the two sets of conditions importantly controlling for other comorbidities as well, and perhaps even introducing a little more epigenetics into proceedings bearing in mind that your genes might not necessarily be your destiny. Going back to the whole endophenotypes thing, I also wonder about the involvement of things like the MET gene work and any differences in early presentation (i.e. regression) as potentially important factors. Noting also that as per the example of the autoimmune condition, coeliac (celiac) disease, genetic predisposition also often requires an environmental counterpart for the disease to become fully evident. Dr Becker's paper on SES, autoimmune disease and autism** kinda hints at something similar with some discussion on the hygiene hypothesis and how we might actually need that environmental exposure in some cases.

While writing this post, I was taken back to another researcher with an interest in the genetics of the immune system with autism in mind, the late Reed Warren, and his papers going back 20+ years now on things like the C4B null allele and various studies on other immune-related functions in autism. I'd like to think that we have come some way in the intervening period in terms of technology, methods and realisation at just how complicated our genes and immune system are both with autism and the more general population in mind.

Granted we aren't really any nearer to identifying the underlying issues as to why autism presents and sometimes presents alongside autoimmune conditions, but I suppose at least it is now generally recognised that autism can present alongside issues with immune function and those issues might, just might, be one key to knowing a little more about some of the aetiology and nature of autism.

* Becker KG. Male gender bias in autism and pediatric autoimmunity. Autism Research. March 2012.
DOI: 10.1002/aur.1227

** Becker KG. Autism, autoimmune disease and socioeconomic status. Autism - Open Access. March 2012.
DOI: 10.4172/2165-7890.1000104