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Role of the Innate Immune Response in Celiac Disease with Comments by Roy Jamron

Celiac.com 04/10/2006 - This study looks at innate immune response to gliadin. The innate immune system responds to gliadin inducing zonulin release and increasing intestinal permeability and may be a factor in the onset of celiac disease, but I question if this leads ultimately to the Ag-specific adaptive immune response seen in patients with CD. This innate response fails to explain why one identical twin may have celiac disease and not the other. Both of the twins as well as people not even susceptible to celiac disease would presumably have this same innate response to gliadin. I again urge celiac disease researchers to consider gluten-internalizing bacteria as the necessary trigger for the onset of celiac disease. The presence or absence of such bacteria does indeed offer an explanation as to why one twin gets celiac disease and not the other. Zonulin does not.

In the commercial supplement product, Glisodin, the properties of gliadin have, in fact, already been used for the last few years to facilitate the delivery of the antioxidant enzyme superoxide dismutase (SOD) protecting it from digestive acids and getting it through the intestinal mucosa, probably taking advantage of the zonulin effect. Aware of celiac disease, the developer of Glisodin tried to use other peptides as a carrier of SOD, but the only gliadin was effective. Unfortunately, this denies celiacs the benefit of using Glisodin to treat oxidative stress.

Abstract of Study:

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J Immunol. 2006 Feb 15;176(4):2512-21.
Gliadin Stimulation of Murine Macrophage Inflammatory Gene Expression and Intestinal Permeability Are MyD88-Dependent: Role of the Innate Immune Response in Celiac Disease.
Thomas KE, Sapone A, Fasano A, Vogel SN. Department of Microbiology and Immunology.

Recent studies have demonstrated the importance of TLR signaling in intestinal homeostasis. Celiac disease (CD) is an autoimmune enteropathy triggered in susceptible individuals by the ingestion of gliadin-containing grains. In this study, we sought to test the hypothesis that gliadin initiates this response by stimulating the innate immune response to increase intestinal permeability and by up-regulating macrophage proinflammatory gene expression and cytokine production. To this end, intestinal permeability and the release of zonulin (an endogenous mediator of gut permeability) in vitro, as well as proinflammatory gene expression and cytokine release by primary murine macrophage cultures, were measured.

Gliadin and its peptide derivatives, 33-mer and p31-43, were found to be potent inducers of both a zonulin-dependent increase in intestinal permeability and macrophage proinflammatory gene expression and cytokine secretion. Gliadin-induced zonulin release, increased intestinal permeability, and cytokine production were dependent on myeloid differentiation factor 88 (MyD88), a key adapter molecule in the TLR/IL-1R signaling pathways, but were neither TLR2- nor TLR4-dependent. Our data support the following model for the innate immune response to gliadin in the initiation of CD. Gliadin interaction with the intestinal epithelium increases intestinal permeability through the MyD88-dependent release of zonulin that, in turn, enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa. There, the interaction of gliadin with macrophages elicits a MyD88-dependent proinflammatory cytokine milieu that facilitates the interaction of T cells with APCs, leading ultimately to the Ag-specific adaptive immune response seen in patients with CD.

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2 Responses:

 
Kodi
Rating: ratingfullratingfullratingfullratingfullratingfull Unrated
said this on
27 Oct 2007 8:42:47 AM PDT
Great article! I wonder if any celiac patient could have an adverse reaction to GliSODin, or if it is even a theoretical possibility.

 
Gene Tinsley

said this on
09 Oct 2009 4:11:43 PM PDT
what a great site and informative posts, I will add a backlink and bookmark your site. Keep up the good work!




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I will just share an experience I had..... I went to a steak house where there weren't a lot of safe options for me. So, I decided just to order a drink and eat later. I asked the bar tender about how they made their margaritas - fresh lime juice, fresh orange juice and gluten free tequila. gluten-free all the way. My husband went back to order for me and noticed that the bartender was juicing the limes and serving bread to the customers at the bar at the same time. I would have totally drank that margarita had he not seen him doing that. I decided to skip the margarita because of the high chance of CC

If you're going to continue to push for a diagnosis stay on gluten! A break could lead to a false negative. It's a lot harder to go off it and then go back on...

I still prefer steaming, but I wash my white rice throughly. I purchase California rice which has a lower level of arsenic. Moderation is key to most everything! ?

I eat pretty much grain free just fine, I eat fats instead. But on a side note I posted some specialty and grain free options as of late in the food alternative page where I list companies and food product alternatives. I honestly just welcomed bread back into my life, I found a company that makes grain free bread out of nut flours. Given you have to toast the dang bread to use it well but seems to work decently. Pasta there are carb free versions out there, and there are ones made with quinoa, buckwheat, or other grains, I even know one company that makes nut flour based ones. You can get these gluten-free options and avoid the rice. As to levels of arsenic they do test foods for these, and all should be safe, the trace amounts and the sheer amount you would have to eat to get effected is staggering, a bit of rice will not hurt you regardless if your concerned I know gluten-free watchdog does arsenic testing on products you could check and find the "safest ones" for your concerns.

I've forgotten them, just remember the good stuff. Weekends in Baja or Vegas or up Pacific highway to see the Redwoods and Frisco. Watching the sunrise at Mount Soledad and watching it drop into the Pacific in the evening. Carne Asada Burritos on Garnet* Solana beach ale* Gorgeous women entranced by my exotic accent, humboldt county weed, raves at the romper room, *1.99 are you out of your mind Denny Breakfasts, Christmas on the beach, *Beers in the gaslamp quarter. I need one of these * which by the power of my imagination have magically become gluten free AANNNYWAAY... Arsenic in rice. Yeah.