Is Gluten Safe for Anybody?

Celiac.com 11/28/2020 - Non-celiacs show Interleukin 15 production when challenged with gliadin peptides. A recent study by a team of Spanish researchers puts the world on notice that gluten may trigger adverse reactions in both celiacs and non-celiacs alike.  The research team was made up of Doctors E.  Arranz, D. Bernardo, L. Fernandez-Salazar, J.  A.  Garrote and their colleague S.  Riestra, all based in Spain.  

According to the current medical wisdom, innate immunity to gluten plays a critical role in the development of celiac disease.  This innate immune response is caused by a reaction to the ‘toxic’ gluten peptides that are mediated by a chemical in the white blood cells called interleukin 15, which stimulates these cells to react against foreign proteins like the 19-mer.  The reaction is independent of genetic HLA markers associated with celiac disease.  This causes epithelial stress and triggers the intraepithelial lymphocytes to turn into natural killer (NK)-like cells, which then causes enterocyte cells to die resulting in a compromised permeability of the cells lining of the gut…and, violà, celiac disease! 

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It is by breaching this intestinal lining that peptides such as the 33-mer, come into contact with the lamina propria, which triggers general immune reactions.  

The specific response in celiac disease has been pretty well documented, but until recently, no one had described any differential factors between people with celiac disease and those without.  

Since the toxic 19-mer triggers its damaging effects independent of the celiac associated HLA markers, researchers wondered whether the innate immune response was common in people with and those without celiac disease.  They wondered whether the adaptive response is found only in those susceptible to celiac disease.  

The gliadin-challenged patients with celiac disease who were on a GFD, showed increased nitrite levels, which those without celiac disease did not show.  Only patients with celiac disease showed modifications to what are called adaptive mediators (STAT1, STAT3, IFNc).  

The samples of those celiac patients on a gluten-free diet showed interferon levels that were 80 times higher than those without celiac disease, along with a slightly higher production of nitrites.  

This appears to be the first time that researchers have described an interleukin 15-mediated innate response to gliadin and gliadin peptides in people without celiac disease, as well as the first time they have described an IL15-mediated innate response to the ‘non-toxic’ deaminated immuno-dominant 33-mer peptide.  

What this all means is that, for the first time, scientists have documented harmful effects of gluten on people without celiac disease.  This hypothesis seems to be born out by the fact that all individuals who took part in the study, both those with and those without celiac disease, showed an innate immune response to gluten, though only those with celiac disease showed an adaptive immune response to gluten.  

Clearly, before doctors can draw any hard and fast conclusions, they will need to do more studies on larger groups.  

The research team also suggests that people with celiac disease have a lower threshold for triggering an adaptive TH1 response than do non-celiacs.  

The reason for the differences in threshold levels between celiacs and non-celiacs might be the result of higher levels of immune reactions in celiac patients compared to those without celiac disease.  That’s one possibility.  

The difference in threshold levels might also have to do with some kind of defect in permeability of the gut membrane in those with celiac disease, or a greater immune sensitivity to equivalent quantities of toxic gliadin fractions which might come from a higher density of interleukin 15 receptors in patients with celiac disease.  

Source: Gut 2007;56:889–890