Sunday 15 January 2012

Autism and SPAD

The NIH very recently issued a press release about some exciting advances being made in the field of cold urticaria, an allergic disease brought about in response to cold temperatures. The release got my attention because it highlighted the role of the immune system and in particular immune deficiency, with findings which might have implications far beyond the original condition under investigation.

Connected, the latest paper from Harumi Jyonouchi and colleagues* alluded to in my recent Sutterella post has, at the same time, been popping in and out of my mind over the past few days. Dr Jyonouchi's research has been discussed before on this blog and this latest offering is along similar lines with a couple of important additions, most notably on a condition called specific polysaccharide antibody deficiency (SPAD). For those like me who are perhaps not acquainted with SPAD, a good overview is included as part of this paper. In short it is immunodeficiency (hence the tentative connection with the NIH research); the inability to make antibody to polysaccharide encapsulated organisms and is normally treated by IVIg infusion. I might add that Jyonouchi seemingly has an interest in SPAD and has discussed SPAD and autism previously.

The paper in question is open-access but a few interesting points are summarised:

  • Eight children diagnosed with autism and comorbid SPAD were compared against children with ASD but not SPAD (n=39), asymptomatic controls (no ASD and no SPAD, n=37) and children with SPAD but not ASD (n=12).
  • A range of measures were analysed linked to innate and adaptive immune response and cytokine production by PBMCs in response to various stimuli.
  • The results: some interesting data on something called food protein induced enterocolitis syndrome (FPIES), a non-IgE-mediated food hypersensitivity primarily linked to milk or soy. FPIES was present in 5/8 (62%) of the ASD/SPAD group and by coincidence, 25/40 (62%) of the ASD/no-SPAD group. The ASD/SPAD group were screened for coeliac (celiac) disease and other GI conditions and everything came out negative. 
  • Participants in the ASD/SPAD group seemingly produced different patterns of cytokines compared with the other groups. So lower in response to agonists of Toll-like receptors, were IL-6, IL-23 and IL-1b (beta) (pro-inflammatory cytokines) compared to all other groups. IL-10 levels in the absence of a stimuli were lower in both ASD groups compared to controls. 
  • Transcriptional profiling of PBMCs showed that over 300 genes were either up- or down-regulated in the ASD/SPAD group compared to controls. Gene expression of CCL2 (noted in their previous study) may point to a constant activation signal potentially linked to things like inflammation.
  • The conclusions drawn from the data are (a) there may be a subset of children with autism whose behavioural presentation may be linked to underlying issues with the immune system and how it reacts to challenges and (b) SPAD can coexist alongside autism.

There are a few comments to make on the collected data presented outside of just the relatively small participant group. Whilst not being an expert on FPIES, I do wonder about the overlap between this condition and the previous findings from Tim Buie for example on lactose intolerance in some cases of autism. I'm not saying that they are one and the same because they are not; just that more generically issues with milk and its components seem to follow autism as per the studies on use of a milk-free diet and predictors of functional bowel problems like constipation.

I touched upon IL-10 in relation to autism in the Sutterella post and that as an anti-inflammatory cytokine, IL-10 is already in the frame in autism research including its potential link to MET gene variants. IL-6 showed up recently in a post looking at the immune profile during pregnancy and risk of autism among other things; IL-23 takes us back to some recent MIND Institute findings linked to social behaviours. I am slightly cherry-picking here with these associative studies but there is some interest there.

The use of IVIg in cases of autism has some history and on the back of studies like this, I suspect it will gain even more clinical favour as time goes by (although note that I am not giving medical or any other advice). Looking around at what else is included in the medicine cabinet in relation to autism, I am struck by how an old favourite like melatonin might also have some interesting immune effects in relation to the current and other studies. So those upregulated CCL2 chemokines.. melatonin might just do something here, increasing levels of IL-10... maybe something here too. Like all medication, the clinical use discussed on the PIL does not mean that is all it might do.

Immune function in relation to autism is a very complicated thing. What studies like this show is that autism is not protective against developing other conditions and that just because someone is diagnosed with autism does not mean that clinical investigations should cease and desist.

To finish a spot of Pavement bringing back some Gold Soundz. Cue the Santas, bows and arrows.

* Jyonouchi H. et al. Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): Case study. Journal of Neuroinflammation. January 2012.

2 comments:

  1. Hi Paul Whiteley -

    I haven't trudged through the latest Jynouchi paper yet, but the last one from her group I loved because it described my son to a T; altered behaviors post sickness and a crazy inability to combat infections, a child that caught every sickness that came around.

    I'm a little torn on the Jyonouchi approach, clearly we need more work understanding phenotypes, but man, that stuff was so dense that it was very difficult to get my head around.

    Lastly, the differential cytokine profiles by phenotype referenced by Jynouchi make this area an even bigger mess than before just trying to get the MIND studies to come together.

    Nice post.

    - pD

    ReplyDelete
  2. Many thanks pD.

    I am very much in agreement with you about the complicated, multiple directions that the collective Jyonouchi and MIND studies on the immune system seem to be sending everyone in. Is it pro-inflammatory, is it immune deficiency..? perhaps very much different for different people.

    Despite the impressive array of studies published by the MIND Institute, Jyonouchi and colleagues have a little bit of an edge for me at the moment because of the way they seem to talk more about immune (and other) comorbidity and the similarities/differences to other seemingly unrelated conditions outside of autism.

    I say this because it is all too easy to assume that immune findings 'are autism' when, at the moment, the range of investigations is just not there to prove a blanket statement like this. The post on folate autoantibodies just posted(!) perhaps reiterates this issue.

    ReplyDelete

Note: only a member of this blog may post a comment.