Gluten-free diet, immune response and autism?

I was heartened to see the publication of the paper by Giacomo Caio and colleagues* (open-access version available here) discussing how the use of a gluten-free diet has a pretty obvious effect on the presence of IgG anti-gliadin antibodies in cases of non-coeliac gluten sensitivity (NCGS). To quote from the Caio paper: "Anti-gliadin antibodies [AGA] of the IgG class disappear in patients with non-celiac gluten sensitivity reflecting a strict compliance to the gluten-free diet and a good clinical response to gluten withdrawal". NCGS is a real interest of mine and for any UK pharmacists out there, you can access an article I helped write about it not so long ago (see here).

For those who might need a little background, antibodies to something like gliadin (part of the protein gluten derived from various cereal produce) represent the ever-vigilant immune system labelling gluten as 'foreign' and taking appropriate biological action. You might say, well gluten is foreign (as opposed to self i.e. the body) and so should be immune labelled in such a way. But if this were the case then everyone would be mounting an immune response to gluten and well, then we probably wouldn't be consuming it in the first place.

Also have a think about it... how does the immune system come into contact with something like gliadin in the first place? We eat foods containing gluten and after some chopping up by various enzymes in that long dark corridor we call the gastrointestinal (GI) tract, we are supposed to derive nutrition from such feasts. Gluten and other proteins/peptides should in the most part be confined to the GI tract and hence not meeting immune function aside from the odd brush with the various mucus membranes in the GI tract. So, why does the immune system start to recognise said proteins and mount a response to them via the production of antibodies in some people? I'll come back to this question shortly.

Anyhow, extrapolating the Caio results to instances where IgG antibodies to gliadin have been reported in the scientific literature, we end up with some intriguing suggestions when it comes to cases of autism. Indeed, we also arrive at some interesting work in other behaviourally defined conditions including schizophrenia (see here) but I'm gonna leave that side of things for now.

The finding by Caio that "AGA IgG persisted positive only in 3 (6.8 %) out of the 44 NCGS patients tested after 6 months of gluten withdrawal" to me suggests something really rather important when one takes on board the AGA findings reported in cases of autism by Lau and colleagues** and de Magistris and colleagues***. Not only does it suggest that some cases of autism might fall into that NCGS category but also that there is appropriate justification to implement a gluten-free diet in order to reduce that immunological load towards gliadin. That is, if one is to ensure that a label of autism does not equate to health inequality in this area...

There is another interesting detail within the Caio paper with regards to their comparisons to participants who presented with the more classical gluten-related condition, coeliac (celiac) disease insofar as those with NCGS and their intestinal presentation. Another quote: "Small intestinal biopsy, tested in all of them on a gluten-containing diet, showed either a normal mucosa (Marsh 0) (n = 26) (58 %) or mild abnormalities (n = 18) (42 %), with an increased number of intra-epithelial lymphocytes (Marsh 1)". If you click on the link above to a mega-post I wrote on 'what is coeliac disease' you'll get a flavour for what the Marsh criteria are. What the Caio results suggest is that the characteristic mucosal findings normally related to a diagnosis of coeliac disease were not present in the NCGS group, which interestingly enough was also similar to the findings from Ludvigsson and colleagues**** in cases of autism which I talked about in a previous post (see here). Perhaps even more evidence that some autism might fit into that NCGS category?

Going back to that question of what makes the immune system react to gliadin in some people and not others, well, again I'm leaning towards some possible effect from issues like gut hyperpermeability (the so-called leaky gut) as being one possible mechanism. I'll direct readers back to another of my mega-posts on all-things leaky gut and autism for some further details about this (see here) but as yet, I can't for sure provide you with details of a specific biological mechanism of effect outside of the present generalisations.

Still, I'll reiterate that the Caio findings are potentially very important to research examining the link between some cases of autism and dietary components like gluten (or gliadin) and certainly add to the speculation that NCGS may be a valid clinical entity for some on the spectrum.

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* Caio G. et al. Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity. BMC Gastroenterol. 2014 Feb 13;14(1):26.

** Lau NM. et al. Markers of Celiac Disease and Gluten Sensitivity in Children with Autism. PLoS One. 2013 Jun 18;8(6):e66155.

*** de Magistris L. et al. Antibodies against food antigens in patients with autistic spectrum disorders. Biomed Res Int. 2013;2013:729349.

**** Ludvigsson JF. et al. A nationwide study of the association between celiac disease and the risk of autistic spectrum disorders. JAMA Psychiatry. 2013 Nov;70(11):1224-30.

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Caio G, Volta U, Tovoli F, & De Giorgio R (2014). Effect of gluten free diet on immune response to gliadin in patients with non-celiac gluten sensitivity. BMC gastroenterology, 14 (1) PMID: 24524388