Markers of autoimmunity and autism

Immune function, in all its guises, seems to be of some interest to autism, or at least some cases of autism. PubMed is littered with papers about immunity, autoimmunity and various biological processes pertinent to immunity all related to autism. This recent paper for example reported higher levels of anti-ganglioside antibodies in autism (normally assosociated with Guillain–Barré syndrome) .

A lot of the more recent work seems to be coming out of the MIND (Medical Investigation of Neurodevelopmental Disorders) Institute and collaborators based at UC Davis and includes researchers such as Paul Ashwood, Judy Van der Water and Irva Hertz-Picciotto to name but a few. A few choice paper abstracts from the MIND team are here, here and here.

Why is the immune system seemingly so relevant to cases of autism?

Well that is a question indeed. A question also whether the immune system is 'causative' of autism or findings are just epiphenomenal. I can't cover the spectrum of immune findings in autism in just one post - so I won't try. Instead just zooming in on one little section potentially tied into a smaller sub-section on autoimmunity and diet and autism.

Diet is an obvious starting point given that quite a few people with autism have been reported to show some 'change' in their core and/or peripheral functions following the adoption of diets such as those excluding gluten and casein. The research in this area is still fuzzy and subject to quite a lot of debate. Diet 'may' correlate with some behavioural changes but no-one really know the reason(s) why and the effect is most certainly not a universal one. The involvement of the immune system in relation to diet has quite a long history. One need only look at coeliac disease to know that.

A recent paper has appeared describing a specific elevated autoimmune response in autism. The main focus of the paper was an autoantibody response to tissue transglutaminase(-2) in autism. tTG (to those in the know!) is an interesting target for the immune system. I will try and explain as best I can. Tissue transglutaminase is an enzyme involved in a reaction that, I will admit I know very little about, dealing with proteins. It is ubiquitous in that it covers quite a few different functions related to blood and skin chemistry for example and has been linked to various conditions such as Alzheimer's disease.

The current study suggested that serum levels of IgA antibodies to tTG were elevated in autism vs. controls. IgA antibodies are generally related to mucosal immunity - anywhere where there is a mucus membrane. IgA antibodies to tTG are also a primary finding in coeliac disease related specifically to the gut (the diet connection). Importantly also in this recent paper, the authors suggested that such elevated IgA antibodies to tTG in autism correlated with the expression of a specific set of genes related to the immune system, falling under the HLA. HLA also shows some connection to coeliac disease.

What does this all mean?

Well, without trying to either simplify the results or make too much of them, the authors suggest that this is evidence for problems in brain chemistry related to synapses et al. That is a perfectly logical conclusion to make from their data. I have to say that their results might also imply something else related to autism and coeliac disease. My reasoning: in their discussion, the authors suggest a connection to coeliac - the only problem is that when it comes to other markers of coeliac disease, there was no information on whether or not their autism group potentially had coeliac disease or not.

We have a situation therefore where roughly the same autoimmune findings seen in coeliac disease were found in autism, but no information is available as to whether the participants with autism presented with the more usual endoscopic markers of coeliac disease. There is potentially an awful lot more to the immune system and autism so be prepared to see other future posts on the subject. You have been warned!