Friday, 7 December 2012

Immune function: a critical role in autism?

The headline to this post is not my own but rather taken from the conclusions of the study published by Vishal Saxena and colleagues* (open-access) who undertook some computational analyses of some of the various genomic findings detailed in cases of autism spectrum disorders (ASDs).

Rather than me bore you with all the details of their study, I'll instead refer you to the ScienceDaily entry for this study (see here) which gives a far better overview than I possibly could. In essence it all boiled down to systems biology (looking at genes and their various pathways) and the application of something called Linkage-ordered Gene Sets (LoGS) which "takes pre-existing gene sets and ranks them in terms of their importance in autism".

As per their paper and the accompanying press release suggest, genes involved in immune function featured heavily in their results. In particular was the suggestion of some involvement for genes related to cytokine activity (see this post), the interferons (see this post) and the genetics of virus response (see here). Also appearing in the top 20 pathways turned up was an old friend, glutathione transferase activity, which one has to wonder might fit in with some other results on glutathione and autism which were published in recent months (see here and here). Just speculating...

There's other possibilities arising from the data produced by Saxena et al, some of which the authors start to discuss with reference to things like autoimmunity, which at least one of the co-authors has kinda hinted at before in the famous "significantly over-represented" paper discussed not so long ago. That and mention of the words "in-utero infections" and "mouse models of autism" which 'might' take us back to the work of Paul Patterson and colleagues (see here).

Regular readers might know that I'm not exactly enamoured by the results of the multitude of genetics studies which have been completed with autism in mind given both the heterogeneity of the condition and also the seeming lack of appreciation that autism does not exist in a vacuum but instead might significantly elevate the risk of other conditions co-occurring. As we also found out recently, we all carry quite a few mutations around with us, whether diagnosed with autism or anything else and even those don't necessarily mean anything. That and the rise of epigenetics... What I am however drawn to in this paper is the focus on the 'bigger picture' outside of just genes encoding for one protein; as the study authors put it in terms of pixels and zooming out. The question now is: who are these results most pertinent to on the autism spectrum and is this yet more evidence for the autisms?

But enough for now, aside from a final quote from the paper: "The results presented in this paper show that immune function may play a critical role in the genesis, development, or manifestation of autism". Who am I to argue?


* Saxena V. et al. Structural, genetic, and functional signatures of disordered neuro-immunological development in autism spectrum disorder. PLoS ONE. 2012; 7: e48835.

---------- Vishal Saxena, Shweta Ramdas, Courtney Rothrock Ochoa, David Wallace, Pradeep Bhide, & Isaac Kohane (2012). Structural, genetic, and functional signatures of disordered neuro-immunological development in autism spectrum disorder PLoS ONE


  1. I read the article also and was hoping you would comment on it. It is fascinating stuff and I am waiting for someone to follow up with population studies that may connect some of the dots and help us sort out some of the many subgroups. Also, ANYTHING that can give us clues on the immune system battles we face is welcome.

  2. Thanks for the comment Teresa.

    It is indeed fascinating stuff and despite my misgivings about the current state of the genetics research on autism, kudos to the authors for looking beyond just autism insofar as what else identified genes might be doing and related to.