Sunday 28 August 2011

More autism and bowels and immune system

I'm sorry. Once again I am brought back to the topic of autism and gastrointestinal (GI) symptoms in this post. I am sure that some readers might be getting pretty fed up with the amount of times that I have talked about functional bowel symptoms or more persistent GI co-morbidity in relation to autism. It's not that I don't try and talk about other things, but the research just keeps pulling me back to this area, so please stay and humour me.

The research in question is this paper* by Harumi Jyonouchi and colleagues on autism, bowel symptoms and the immune system. I have quite a lot of time for Dr Jyonouchi and her various research efforts in autism down the years. A quick taste of some of the research she has been involved in is here, here and here. What she and her team provide in their various studies is a route through which elements such as diet, the immune system and GI dysfunction all congregate together, at least in some cases of autism spectrum conditions.

The recent paper adds to the collected works by suggesting some involvement for the way the innate immune system is able to cope with potential pathogens and how this might tie into behavioural presentation. I should perhaps back up a little and provide some information on the innate immune system which is basically our first line of defence against infection. I suppose one could suggest that the innate immune system is the first-line, bunker-buster that tries to smash infection as soon as it is detected, and the other branch, the adaptive immune system is the precision, laser-guided missile which targets specific pathogens (and importantly remembers them for next time). The memory bit however is still something under investigation as shown in this recent paper.

The main aims and results from the recent paper:

  • Three groups of participants were recruited: ASD/Infection (children with a diagnosis of autism spectrum disorder confirmed by ADI-R and/or ADOS with 3 occurrences or more of behaviour change following infection, n=30), ASD/No Infection (no behaviour-infection relationship documented, n=28) and controls (asymptomatic, n=26).
  • Various parameters were studied including: the presence of atopic disease (IgE-mediated), various cytokines, transcription profiling (I will come to this shortly).
  • Chronic functional GI problems were more commonly found in the ASD/Infection group (63%). Such problems were not due to coeliac disease, inflammatory bowel disease or other known precursors which were looked for.
  • Seven of the GI/Infection group (23%) were diagnosed with immunodeficiency (antibody deficiency syndrome). All were treated with intravenous immunoglobulin (IVIG).
  • When sub-dividing the ASD/Infection group into whether GI symptoms were present or not, where present, measured levels of the cytokine IL-6 (when incubated with various agonists) were significantly lower when compared to controls. Various other cytokines (proinflammatory and counter-regulatory) were also altered.
  • Transcription profiling, measuring the expression of genes, in peripheral blood monocytes, suggested that many more genes were up-regulated or down-regulated in the ASD group vs. controls. Indeed, where the ASD/Infection+GI symptoms group were examined, the greatest disparity was noted compared with both controls and those ASD/No infection. One of the more important up-regulated genes was that related to the chemokine, CCL2, potentially indicative of CNS inflammation. I wonder what effect this might have on that blood-brain barrier?

There are many more findings from this paper but I am fast approaching the outer limits of my competency. The authors summarise the main findings as being the identification of a distinct ASD phenotype, characterised by infection affecting/being affected by behavioural symptom presentation, the presence of functional bowel problems, abnormalities of the innate immune system indicated by functional and transcript profiling. It should be noted that the absolute numbers of children included in this study was relatively low. This will have obvious effects on how applicable the results might be to the wider autistic (and beyond?) population but that's why we have scientific replication.

Whilst some of the results sound pretty scary (immunodeficiency), I think there are a lot of positive to take from this work. I feel I am constantly talking about how autism is not autism but rather autisms and the concept of different phenotypes/sub-groups. What this work implies is that there may be several, measurable differences according to symptom presentation which provide some potentially tangible targets to focus on. The collected immune system findings in relation to autism are complicated and often at odds with each other (overactive vs. underactive). I don't see this as a problem; it suggests that just as we have a 'spectrum' of behavioural presentation, so we might also have a spectrum of biological/genetic presentation also. God knows with all the various genetic findings recently, we know that autism is just as complicated as not-autism. Although perhaps not the primary outcome, this recent paper also points to things which could be done to 'influence' some of the underlying biological issues. Whether these would have any knock-on effects for presented symptoms remains to be seen.

To end, completely and unashamedly nothing to do with this post, the genius of Elvis on what to do in Las Vegas.

* Jyonouchi H. et al. Children with autism spectrum disorders (ASD) who exhibit chronic gastrointestinal (GI) symptoms and marked fluctuation of behavioral symptoms exhibit distinct innate immune abnormalities and transcriptional profiles of peripheral blood (PB) monocytes. J Neuroimmunology. 2011

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