Friday 28 April 2017

Could a silent virus trigger celiac disease? Scientists say...maybe...

The gluten-free lifestyle has moved from relative obscurity to mainstream use.  For most individuals, a gluten-free diet will be a passing obsession (although one which may result in increased attention to what is in food - which is a very good result) but for those with celiac disease it is a welcome societal movement.  Celiac disease is an autoimmune condition which presents with gastrointestinal distress (pain, bloating, cramping), steatorrhea/diarrhea and malabsorption.  Sounds a bit like IBS, right?  Many of the clinical symptoms of celiac disease and IBS are identical, making a true celiac disease diagnosis challenging for both patient and practitioner.  A person with true celiac disease has a specific and measurable autoimmune response to the ingestion of dietary gluten.  IBS symptoms are often non-specific (i.e. varying severity, length, location, etc.) and worsen with a virety of triggers (gluten may be a trigger for IBS symptoms, but other dietary (lactose, soy, fructose) and lifestyle factors (chronic stress) influence this condition).  Fortunately, diagnostic tests for celiac disease are becoming more common and often begin with a simple blood analysis - unfortunately, however, IBS has not lent itself to reliable diagnostic measures.  Several specific criteria are used to confirm a diagnosis of celiac disease, although every body and everybody is different: 

1) HLA-DQA1 or HLA-DQB1 gene variants (this is very important - if you do not have the 'celiac gene mutation' you do not have celiac disease; non-celiac gluten sensitivity is a related condition which does not invoke a true autoimmune response but has been described as a gluten-related inflammatory response)
2) Elevated antibody levels (tTG, IgA, IgG - these are the 'gluten antibodies' which can be quantified in the blood and used as a diagnostic marker for the autoimmune condition)
4) Vitamin A, D, E and K deficiencies (fat-soluble vitamins are less readily absorbed due to intestinal damage)
5) Damaged (atrophied) intestinal lining confirmed by small bowel biopsy
6) Environmental trigger resulting in decetable immune response

Common factors 1-5 are easily tested for and confirmed by a gastrointestinal specialist - most of them are quantifiable and/or visually informative.  The 'environmental trigger' aspect of celiac disease (6 listed above) has remained the most elusive requirement for disease onset.  How do we even know that an environmental trigger is important?   Scientists agree that environmental risk factors are likely to be a cause of consideration based (so far...) purely on statistics.  Celiac disease occurs globally in 1 out of 100 people.  However, only 3-4% of individuals who carry the HLA-DQA1 or HLA-DQB1 gene variants ever develop celiac disease - what happens or does not happen to the other 96-97% who never progress?  These values are reported in a recent study published in Science which reports the first experimental observation of celiac disease onset after exposure to a known environmental trigger.  Their study, titled 'Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease' describes a controlled experiment in which genetically susceptible mice, living on a gluten-containing diet but showing no clinically diagnostic celiac disease symptoms, are exposed to a known reovirus.  Onset of celiac disease after viral exposure was confirmed by a measurable increase in immune response pathways, specifically those which promote the production of T-cells (immune cells) which specifically respond to the gluten antigen.  This particular immune response pathway is triggered by HLA-DQ2 and HLA-DQ8 molecules, which are coded for by the HLA-DQA1 or HLA-DQB1 gene variants.  

So, the mice had these genes and consumed a gluten-containing diet but did not show signs of celiac disease prior to viral exposure.  What this study shows is that the externally applied environmental factor (the reovirus - which is avirulent and causes no 'viral symptoms') has 'turned on' the mutated gene (just like a ligh switch).  When the gene variant is 'turned off,' it is still there but it is not physiologically active, whereas when the gene is 'turned on' downstream physiological changes have been shown induce disease progression.  Now, would the mice have eventually developed celiac disease if they had not been exposed to the reovirus?  Maybe.  Would they have developed celiac disease from some other environmental trigger?  Maybe.  What this study provides is only one piece of the enormous jigsaw puzzle describing celiac disease - and most of the pieces are still scrambled in the box!  There are likely thousands of additional environmental triggers which influence disease progression, and not every genetically susceptible individual who encounters a reovirus will go on to develop celiac disease.  However, direct demonstration and observation of environmentally triggered change in gene expression promoting the development of celiac disease is a HUGE step towards understanding the complicated relationship between food and the immune system.  I'll raise a glass of (gluten-free) beer to that!


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