Paediatric autoimmune enteropathy: I did not know that

Consider this post one of my 'other musings' entries on this blog and also a slightly more descriptive post than usual.

The source paper today is by Singhi and colleagues* discussing the pretty rare condition paediatric autoimmune enteropathy (AIE), which I have to say was a bit of an eye-opener for me. Associated with protracted diarrhoea (sorry if your eating at the moment), weight loss and gut mucosa damage, the crux of the paper by Singhi et al seemed to be that the gut or gastrointestinal tract is a central organ affected by AIE - hence the enteropathy bit of the condition description - but also that "autoimmune enteropathy in children is a heterogeneous disease with protean clinical and pathologic findings". Protean by the way, means readily assuming different forms or characters (yes, I had to look it up).

I say that this is another one of my other musings post, but one of the first people to describe this condition was one Prof. John Walker-Smith** who some people might know from the still quite contentious area of gut physiology and autism*** (see a related post here). Mention of the gluten-free (GF) diet in amongst the AIE literature also piqued my attention, allowing for the fact that such dietary intervention does not seem to help in many cases of AIE**** as it does more frequently in coeliac (celiac) disease.

With my non-expert hat very firmly in place when it comes to AIE and my caveat about not giving medical or clinical advice on this blog, I was rather interested in the condition and so set about looking at some of the related literature around it to share with you. Here goes:

• AIE is a serious condition primarily reported in very young infants. I say serious because in quite a few of the experimental reports of AIE, mortality is, unfortunately, mentioned (see here for an example). 
• Whilst quite a lot of the research literature is focused on AIE in children as a function of the increased likelihood of occurring infancy, there is a body of research suggesting that adults can also present with the condition*****. In some quarters, that adult presentation has been linked to refractory sprue. 
• Boys are over-represented in AIE. 
• Gut epithelial cell antibodies - that is an immune response to the cells lining the gut - characterise this disease. In particular, anti-enterocyte antibodies are reported to be an important part of AIE as per the link with autoimmunity. That being said, anti-goblet (the mucus producing cells) and anti-Paneth (important defender cells of the gut) cell antibodies have also been reported in cases. 
• The autoimmunity link is certainly strong when it comes to AIE as per the varied comorbidity and other autoantibodies tied into presentation******. T-cells, and in particular Th-17 cells, which have been linked on more than one occasion to autoimmune conditions (see here), have been a focal point for the pathology of AIE*******. Indeed to quote the article by Ruemmele et al "Anti-enterocyte autoantibodies .... seem to be of a secondary nature and can no more be considered as directly disease causing".
• Going back to the Singhi paper, the autoimmune element to AIE has very much informed the therapeutic response to AIE and the use of various immuno-suppressing medicines. So starting with things like steroids, treatment can also include cyclosporin (see here********), tacrolimus and cyclophosphamide. Other therapeutic interventions also include anti-lymphocyte immunoglobulin and eventually in some cases, a bone marrow transplant (see here too). I did wonder, in light of the recent-ish news that alefacept - another immuno-suppressive medicine - might impact on the presentation of another autoimmune conditions, type 1 diabetes (see here), whether there may be other treatment options waiting in the wings too.

I'm gonna stop at that with this very descriptive post. AIE is a complicated condition which is both heterogeneous and potentially carrying quite a bit of other autoimmune related baggage. I do get the impression from quite a few sources that in almost 30 years since formal description, some progress has been made on discovering how AIE is expressed and indeed, in treating the condition. One might say that the advent of immuno-suppressive therapeutic options being applied to AIE, has been nothing short of remarkable in terms of long-term prognosis.

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* Singhi AD. et al. Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders. Mod Pathol. 2013 Sep 20. doi: 10.1038/modpathol.2013.150.

** Unsworth DJ. & Walker-Smith JA. Autoimmunity in diarrhoeal disease. J Pediatr Gastroenterol Nutr. 1985 Jun;4(3):375-80.

*** Ashwood P. et al. Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. J Clin Immunol. 2003 Nov;23(6):504-17.

**** Walker-Smith JA. Coeliac Disease and Autoimmune Enteropathy. Developments in Gastroenterology. 1991; 13: 131-136.

***** Freeman HJ. Adult autoimmune enteropathy. World J Gastroenterol. 2008. 14(8): 1156–1158.

****** Akram S. et al. Adult autoimmune enteropathy: Mayo Clinic Rochester experience. Clin Gastroenterol Hepatol. 2007 Nov;5(11):1282-90.

******* Ruemmele FM. et al. Autoimmune enteropathy: molecular concepts. Curr Opin Gastroenterol. 2004 Nov;20(6):587-91.

******** Sanderson IR. et al. Response to autoimmune enteropathy to cyclosporin A therapy. Gut. 1991 Nov;32(11):1421-5.

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Singhi AD, Goyal A, Davison JM, Regueiro MD, Roche RL, & Ranganathan S (2013). Pediatric autoimmune enteropathy: an entity frequently associated with immunodeficiency disorders. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc PMID: 24051695