Immune endophenotypes in paediatric autism

Today I'm serving up the paper by Milo Careaga and colleagues [1] for your blogging delight, who concluded that: "Children with ASD [autism spectrum disorder] may be phenotypically characterized based upon their immune profile." Further that there may be: "several possible immune subphenotypes within the ASD population that correlate with more severe behavioral impairments."

With many thanks to Natasa for the paper, participants - 50 boys with a median age of 3.2 years diagnosed with an ASD and enrolled "through the Autism Phenome Project (APP) study" and who were free of any "major immune modifying medications" - provided a blood sample. A similar process was employed for a smaller group of typically developing (asymptomatic) control group (n=16). Said blood sample went through various processes to harvest peripheral blood mononuclear cells (PBMC) which were then 'stimulated' to provoke an immune reaction via "either lipopolysaccharide (LPS) or phytohaemagglutinin (PHA)." Various cytokines were then assayed for in the stimulated PBMC and results analysed according to immune responses and behavioural outcomes.

Results: as per the opening paragraph, there was potentially something to see in the findings added to a more general role for cytokines in relation to autism [2]. Those children with ASD who presented with a more 'pro-inflammatory' cytokine profile in their stimulated blood results "showed more impaired developmental and behavioral scores, as well as increased problems with sleep and aggression." That pro-inflammatory cluster by the way (n=22) tended to show significantly increased production of cytokines such as IL-6 for example, than those children with autism (n=28) "who displayed a less robust response to LPS." Ergo, perhaps more to see and certainly more investigations required in these days of plural autisms.

I was taken by one particular sentence included in the conclusion of the Careaga paper: "Although immune abnormalities were first described in ASD over forty years ago, no consensus has been reached as to what constitutes clinically significant immune dysfunction in ASD." As per quite a bit of autism research, sweeping generalisations about this, that or t'other 'causing' autism or being part and parcel of autism have been a big contributor to the noticeable lack of progress on knowledge about autism and where required and wanted, what can be done to ameliorate the more disabling aspects including that related to comorbidity (see here). Realisation that 'autism' is probably better described as providing an umbrella term for various different conditions on a genetic and molecular level is making some headway these days (see here) including that linked to immune function (see here for example). This might have important implications for intervention (see here) as per other recent results that I'll be musing over soon.

As part of a broader realisation that immune function and psychiatry probably show a lot more connections than many people first realised (see here), I think we are seeing a shift in knowledge here. As per the Careaga results, the idea that there may be distinct clusters within the presentation of autism linked to immune function, opens up a whole new world of more 'targeted' inspection and intervention which, added to other similar phenotype work (see here), is probably an important direction for autism research...

Music: Duran Duran - Pressure Off feat. Janelle Monáe and Nile Rodgers.

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[1] Careaga M. et al. Immune endophenotypes in children with autism spectrum disorder. Biological Psychiatry. 2015. 10 Sept.

[2] Krakowiak P. et al. Neonatal Cytokine Profiles Associated with Autism Spectrum Disorder. Biol Psychiatry. 2015 Aug 14. pii: S0006-3223(15)00655-1.

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Milo Careaga, Sally Rogers, Robin L. Hansen, David G. Amaral, Judy Van de Water, & Paul Ashwood (2015). Immune endophenotypes in children with autism spectrum disorder Biological Psychiatry : 10.1016/j.biopsych.2015.08.036