Actually the title to this post should really read 'sensitising' rather than 'sensitizing' as a function of my Limey status. No mind, today I'd like to introduce you to two pretty unusual papers which I stumbled across in recent times which have the common denominators of (a) both being about gluten and the possible induction of problems with gluten, and (b) both carrying Marios Hadjivassiliou as part of the authorship team. They're both open-access too.
The first paper is by Currie and colleagues* who concluded that: "Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten". The second paper by Ludvigsson & Hadjivassiliou** in a similar vein suggested that there was a: "very small excess risk for future CD [coeliac disease] in individuals with an earlier head trauma".
Why am I talking about these papers you might ask? Well, outside of any autism-gluten research obsession I might have, I was interested to read about how an issue with gluten might come about as a function of an environmental insult; in these cases, alcohol abuse and head injury. Just however before I stray away from the autism-gluten science, the keen reader might have already spotted the name Ludvigsson, Jonas Ludvigsson, as being one and the same lead author on that 'not coeliac disease but something gluten related' paper in relation to cases of autism (see here for some discussion).
I'm not going too heavily into these papers but it strikes me that there are a few possible connections to be made from the cumulative data. Autoimmunity is the source of some speculation in both papers. The Currie paper speculates that: "autoimmunity may have a role to play in the development of ataxia in patients that drink excessively". Ataxia by the way, refers to a group of conditions which affect motor skills. Similarly, L & H (because they both have particularly long surnames) talk about "an autoimmune response against transglutaminases triggered by the brain injury". The transglutaminases (plural) or at least one of them (tTG) have already been talked about on this blog with reference to the process of coeliac (celiac) disease (see here).
That 'development of autoimmunity' suggestion also leads into another potential commonality across these papers: the cerebellum. Part of the brain long thought to be involved in motor control (as well as other cognitive functions), the suggestion is that "antigliadin antibodies may arise after a cerebellar insult rather than being the cause of it per se" in the alcohol study. The head injury paper provides an equally interesting commentary, if a little less 'proven' by results: "head trauma resulting in cerebral and cerebellar insults may trigger autoimmunity against TG6 which in turn may lead in some genetically susceptible individuals, to the development of CD".
If I've got all my factoids correct, there is a rather interesting hypothesis to test from these collected results. Take an immune system which genetically looks a little like that seen in coeliac disease with regards to those HLA-DQ2 and DQ8 heterodimers. Add an environmental insult which in particular, targets the cerebellum or indeed some other part of the brain. For whatever reason, the exposure to that insult starts to do odd things to "normally shielded" self epitopes such as TG6 which "may result in the immune system reacting to self-antigens in the central nervous system ultimately leading to autoimmunity". Gluten just happens to be one of the external agents to which antibodies also start being produced against as self and other start to become mixed up, and hey presto, you're gluten sensitive.
OK, I know there is still much to do in this area of research and by no means should anyone take such a hypothesis as fact at this point in time. Marios Hadjivassiliou has done a lot of work in the area of extra-intestinal presentation of gluten issues (see here for example***) but we're not yet in a position to start definitively linking all the pieces together just yet. That and the differences between the two papers discussed in this post in terms of what was looked at (antigliadin antibodies vs. patient register details for head injury and/or small intestinal biopsy reports) and how participants were examined, means I am to a large extent comparing apples and oranges.
Still, I do find this line of inquiry to be quite fascinating. I'm also thinking back to the paper by Emily Severance and colleagues**** on how infection with the gondii (that's Toxoplasma gondii) in a mouse model might also be able to invoke an immune reaction to gluten (see here for my take of the study). There's more to come on this blog from Dr Severance, but again, speculations on immune activation through the slightly different environmental process of infection translating into a immunological effect against gluten.
But still the possibility of an acquired sensitivity to dietary gluten...
* Currie S. et al. Alcohol induces sensitization to gluten in genetically susceptible individuals: a case control study. PLoS One. 2013 Oct 15;8(10):e77638.
** Ludvigsson JF. & Hadjivassiliou M. Can head trauma trigger celiac disease? Nation-wide case-control study. BMC Neurol. 2013 Aug 9;13:105.
*** Hadjivassiliou M. et al. Gluten sensitivity as a neurological illness. J Neurol Neurosurg Psychiatry 2002;72:560-563.
**** Severance EG. et al. Anti-gluten immune response following Toxoplasma gondii infection in mice. PLoS One. 2012;7(11):e50991.
Currie S, Hoggard N, Clark MJ, Sanders DS, Wilkinson ID, Griffiths PD, & Hadjivassiliou M (2013). Alcohol induces sensitization to gluten in genetically susceptible individuals: a case control study. PloS one, 8 (10) PMID: 24204900
Ludvigsson JF, & Hadjivassiliou M (2013). Can head trauma trigger celiac disease? Nation-wide case-control study. BMC neurology, 13 PMID: 23927742