An inflammatory autism subtype?

The paper from Harumi Jyonouchi and colleagues [1] (open-access) continues a theme from this author with their suggestion of "an imbalance in the production of inflammatory (IL-1ß and IL-6) and counterregulatory (IL-10) cytokines by ‘flare’ ASD-IS [autism spectrum disorder - inflammatory subtype] monocytes".

Panic on the streets of Birmingham...

'Flare' ASD-IS in this case refers to a coding given to a small participant group (n=24) who were: "defined as those with a history of fluctuating behavioral symptoms following immune insults (mainly microbial infection)" and who experienced: "worsening behavioral symptoms following immune insults, despite the resolution of acute conditions such as viral syndrome (that is, the resolution of other infectious symptoms if associated with a microbial infection, lack of fever, and no other acute physical symptoms associated with immune insults)".

Innate immune system functions (yes, cytokines again) were measured in flare ASD-IS and compared with results from other groups: (i) controls with autism with a history of "non-IgE mediated food allergy (NFA)" (n=20), (ii) ASD/non-NFA controls (n=20), and (iii) "three groups of non-ASD controls (non-ASD/NFA subjects (N =16), those diagnosed with pediatric acute onset-neuropsychiatric syndrome (PANS, N =18), and normal controls without NFA or PANS (N =16))". For those unfamiliar with the term PANS - pediatric acute onset-neuropsychiatric syndrome - this is a term originating from PANDAS (see here) and denotes an important condition bridging the link between infection and psychiatric symptomatology [2]. As if you needed telling...

Authors concluded that: "‘Flare’ ASD-IS PB Mo [peripheral blood monocytes] produced higher amounts of inflammatory cytokines (IL-1β and IL-6) without stimuli than ‘non-flare’ ASD-IS cells". They concluded that their findings: "support parental impression of worsening behavioral symptoms in the ‘flare’ state following immune insults" on the basis of the immune findings also linking in with behavioural descriptions at the time of sample collections.

Whilst including relatively small participant groups, it is the spread of presentations (not just based on diagnosis) which makes this paper stand out. I note that the authors also report that their results may: "indicate a possibility that monocytes from ASD-IS children also have intrinsic defects in regulatory mechanisms of IL-10 production". This is again, potentially important. Although there is still some misconception that cytokines are binary in function (either pro-inflammatory or anti-inflammatory) when the emerging data are suggesting it is very much more complicated than that (see here), the authors are hinting that inflammation with regards to autism may actually be down to issues with the opposing anti-inflammatory response over and above an upregulated pro-inflammatory response. Sort of like a fire tender not carrying enough water to put out a blaze. Indeed, work from this research team had previously hinted as much [3] (see also my previous post on this paper) as have other studies [4].

I am looking forward to seeing this research independently followed-up and reported on to further characterise those people with autism who such results are potentially relevant to. Whether gastrointestinal (GI) symptoms and dietary intervention might also be important factors [5] in such immune responses, also offers some potentially tantalising options for intervention...

Music to close: Rhapsody In Blue.

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[1] Jyonouchi H. et al. Cytokine profiles byperipheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an
inflammatory subtype? Journal of Neuroinflammation. 2014, 11:187

[2] Chang K. et al. Clinical Evaluation of Youth with Pediatric Acute Onset Neuropsychiatric Syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference. J Child Adolesc Psychopharmacol. 2014 Oct 17.

[3] 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. J Neuroinflammation. 2012 Jan 7;9:4.

[4] Estes ML. & McAllister AK. Alterations in Immune Cells and Mediators in the Brain: It's Not Always Neuroinflammation! Brain Pathol. 2014 Nov;24(6):623-30.

[5] Jyonouchi H. et al. Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention. Neuropsychobiology. 2005;51(2):77-85.

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Jyonouchi H, Geng L, & Davidow AL (2014). Cytokine profiles by peripheral blood monocytes are associated with changes in behavioral symptoms following immune insults in a subset of ASD subjects: an inflammatory subtype? Journal of neuroinflammation, 11 (1) PMID: 25344730