Differential Mucosal IL-17 Expression in Two Gliadin-Induced Disorders: Gluten Sensitivity and the Autoimmune Enteropathy Celiac Disease

Anna SaponeKaren M. LammersGiuseppe MazzarellaIrina Mikhailenko, Vincenzo Casolaro, and Alessio Fasano

Int Arch Allergy Immunol. 2010 Apr; 152(1): 75–80.

Hey guys, this article is what is considered a landmark article because it has specifically identified the difference between celiac disease and gluten sensitivity and how specifically how our body responds when digesting gluten.

  • Gluten is the trigger of a heterogeneous set of conditions, including wheat allergy, gluten sensitivity (GS), and celiac disease (CD), that, combined, affect about 10% of the general population.
  • CD, which roughly affects 1% of the general population, is considered an autoimmune disorder because of the presence of highly specific autoantibodies to tissue transglutaminase (tTG), and may lead to the onset of other autoimmune conditions. Besides CD, GS may present with similar symptoms but without anti-tTG autoantibodies or autoimmune comorbidities. CD is a life-long condition that requires rigorous and continuous avoidance of intake of gliadin, the toxic component of gluten, whereas GS can vary in terms of gluten threshold sensitivity and duration.
  • In support of the autoimmune, adaptive nature of CD, there is a strong genetic association with the MHC class II haplotype in CD patients, about 95% of whom carry HLA-DQ2, and the remainder HLA-DQ8. Conversely, only about 50% of patients with GS carry the HLA-DQ2 or -DQ8 haplotype, a percentage slightly higher than in the general population. The diversity of gluten-induced conditions suggests that the immune system reacts to and deals with the triggering environmental factor, e.g. gliadin, in distinct ways. The identification of interleukin (IL)-17-producing CD4+ T helper cells, Th17 cells, has had major impact on understanding immune processes not readily explained by the Th1/Th2 paradigm.
  • Data show that the expression of IL-17, a cytokine that is thought to be involved in inflammatory and autoimmune processes, is elevated in CD but not in GS. Our work confirms and extends the study by Castellanos-Rubio et al. showing gluten-dependent expression of IL-17A in active CD. In addition, combined with the other observed clinical and histological differences, it further supports the idea that CD and GS are distinct entities and that the immune system deals with gluten in different ways, possibly depending on the genetic makeup. Where in GS as well as in wheat allergy the gluten-induced response leads to immunity toward a non-self diet component, i.e. gliadin, in CD a deviated, self-directed adaptive response leads, in addition, to the onset of a full-fledged autoimmune process. In clear contrast to GS, CD results from a complex, as yet undetermined, interplay of increased intestinal permeability, mucosal damage, environmental factors additional to gluten, and genetic predisposition, which involves both MHC and non-MHC genes 
  • In conclusion, here we present for the first time evidence of differential intestinal mucosal immune responses to gluten between CD and GS, further supporting the notion that CD is the only clinical form of gluten reactivity involving autoimmune mechanisms. We conclude that GS, albeit gluten-induced, is different from CD not only with respect to the genetic makeup and clinical and functional parameters, but also with respect to the nature of the immune response. Our findings also suggest that two subgroups of CD, IL-17-dependent and IL-17-independent, may be identified based on differential mucosal expression of this cytokine. 

This article identifies IL-17, a cytokine (a chemical switch that turn on certain immune cells types on and off)  that is thought to be involved in inflammatory and autoimmune process, how this is elevated in a celiac disease patient but not in gluten-sensitive patient. 

And that our immune systems respond differently to gluten. Yes, we to a large part already suspected this, this is one of the first studies that actually proves the differences. In science, explaining things, defining them, understanding how they work and being able to find distinct differences and patterns are huge steps forward in being able to then move forward towards managing and improving our health.

Science is making huge strides, that is a beautiful thing in helping those of us who live with gluten challenges everyday. So much is still to be understood and it is important that if your doctors are unaware of some of this new information perhaps you could print this article for them. They can’t read every journal. 

Staying on top of your health when you live life with gluten challenges is about so much more than just removing some gluten filled food from your diet.

* Here’s my little disclaimer, I’m not a doctor, researcher, immunologist, just someone deeply concerned and trying to help as many peeps as I can make conscious, good, healthy choices for their health and their bodies when living life with gluten challenges. I have not been compensated or obligated to write this article, and as always, all thoughts and opinions are honest and my own!