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  • Scott Adams
    Scott Adams

    Is Cross-Reaction between Gliadin and Different Food and Tissue Antigens a Celiac Disease Myth?

    Reviewed and edited by a celiac disease expert.

    What evidence supports the idea of "cross-reactivity" in people with celiac disease?

    Is Cross-Reaction between Gliadin and Different Food and Tissue Antigens a Celiac Disease Myth? - Petri Dish Spilled Luminol. Image: CC BY 2.0--Jefeter Scudley
    Caption: Petri Dish Spilled Luminol. Image: CC BY 2.0--Jefeter Scudley

    Celiac.com 04/01/2020 - Some people with celiac disease have symptoms even when they follow a gluten-free diet. Even though the most likely culprit in these cases is cross-contamination, or some other type of food sensitivity, some people have suggested that the problem may have to do with certain foods that trigger a celiac-like gut reaction. But, is that really true? 

    A few years back, a team of researchers set out to figure out if such symptoms might come from either cross-contamination with gluten-containing foods, or cross-reactivity between α-gliadin and non-gluten foods eaten as part of an otherwise gluten-free diet. 

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    Researcher Aristo Vojdani, and colleagues with the Immunosciences Lab used ELISA and dot-blot to gauge the reactivity of affinity-purified polyclonal and monoclonal α-gliadin 33-mer peptide antibodies against gliadin and other food antigens often eaten by celiacs who are following a gluten-free diet. 

    The team also assessed the immune reactivity of these antibodies with various tissue antigens. According to their results, these antibodies to cow’s milk, milk chocolate, milk butyrophilin, whey protein, casein, yeast, oats, corn, millet, instant coffee and rice, triggered significant immune reactivity. 

    These results seemed to confirm that certain foods might be "cross-reacting," and triggering celiac-like symptoms in celiac patients on a gluten-free diet.

    Questions About Vojdani Methodology

    Taken at face value, the 2013 Vojdani study would seem to support the idea of otherwise gluten-free foods being cross-reactive, and causing celiac-like symptoms in people with celiac disease.

    However, a 2019 review of that study by Christina L. Graves Ph. D, with the University of North Carolina at Chapel Hill Department of Biology, casts serious doubt on the methodology and findings of the Vojdani study. Ms. Graves' review, 19 Gluten Cross-Reactive Foods Busted Myth, appears at Paleofoundation.com, and she really highlights the flaws in the Vojdani study, and they are many.

    Also, for something as simple as corn zein, "...celiac disease-specific antibodies don’t appear to cross-react to corn zein. The rice/gluten cross-reactive study cited by Vojdani & Tarash 2013 is specific for IgE mediated responses, whose dominant epitopes are different than the epitopes recognized by anti-α-gliadin antibodies presented in this study.

    Graves takes care not to step on too many toes by noting that she is only seeking "to highlight the importance of being rigorous with our own research and reporting within the ancestral health community and to highlight that the rationale for the avoidance of some foods may have arrived through the inflated interpretation of inconclusive results."

    With respect to the types of tests used to show cross-rectivity, Graves adds "The Celiac Disease Center does not currently recognize Enterolabs or Cyrex stool tests for cross-reactivity (or for celiac disease for that matter). [20] Simply, they are “not sensitive or specific enough” and just haven’t held water (yet) in the scientific arena."

    Graves may tread lightly in her comments, but her methodical take down of the Vojdani study casts serious doubt on the study's methods, and conclusions, about cross-reactivity. Moreover, there has been no substantial confirmation of the Vojdani findings since the original publication, and there has, so far, been no credible rebuttal to Graves' finding regarding the study.

    Thus, it is sensible to conclude that Graves is correct, the Vojdani study methods and conclusions are seriously flawed, and that there is no good data to support to claims that cross-reactivity in certain non-gluten foods can trigger celiac-like symptoms in people with the disease.

    Put simply, until we get more convincing study, with solid evidence to the contrary, there is no good evidence to support the idea of non-gluten cross-reactivity in people with celiac disease.

    Edited by Scott Adams



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    Scott Adams

    I do think more research needs to be done in this area, especially in the realm of additional, usually temporary, food intolerance issued triggered most likely by leaky gut around the time of a CD diagnosis, which usually disappear 1-2 years after a GFD. The overwhelming anecdotal evidence indicates they are real, as they were in my case—I could not eat chicken eggs, tomatoes, dairy, etc. for at least 2 years after my GFD. I believe this is the “cross reactive” phenomena, it’s real, and the full nature of it needs to be studied. On an interesting side note I used to get allergy shots from an immunologist for all the exact same things I ended up not being able to eat. My blood tests for food allergies were very high, especially with wheat, and my doctor told me not to eat it every day. I did not listen. It is interesting the list of foods that scored high in my allergy tests became the “cross reactors” in my case. 

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    Guest ANTHONY COLATRELLA

    Posted

    I have just found another article concerning Microbial TTg compared to TTg2 and it found that the Microbial TTg generally favored transamidation over deamidation which would likely lead to lower immunoreactivity of the treated gliadins (GLUTEN) and this preference was increased depending on ph and ratio of enzyme to substrate--so then possibly in food manufacturing the conditions could be controlled to optimize transamidation over deamidation to result in the least immunoreactive product---the question --is the least good enough or are other resulting products ot transamidation a potential problem--???

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    ch88

    Tissue transglutaminase is a enzyme that is found everywhere in the body. It is also used to breakdown food in the intestine. When someone who is Celiac eats wheat, the combination of this enzyme and wheat causes an immune reaction.  

    I don't think microbial Tissue transglutaminase is much different (it at all) from the enzyme found in the body naturally, or the enzyme that is found is all food. From the research I have done I don't think it is a health risk.  

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    Guest059483

    I am going to have to disagree with the article by Christina Graves based on my personal experience with my body. I think that Aristo Vojdani brought some good ideas to the table that many people would have never thought of otherwise. Once I read the study and applied those ideas to my diet fully I saw immediate results, and I have read hundreds if not thousands of comments from people who have also achieved results because of that study. For me the cross-reactive research by Aristo Vojdani confirmed what I already had discovered on my own, that is, a Gluten-Free diet is not always the whole answer for everyone who is diagnosed with Celiac Disease, and it certainly was not in my case.

    I find it hard to understand why people want to discredit research without ever duplicating the study on their own to discredit it properly. How hard would it be for a professional to purchase foods from the super market and test this for themselves, rather than just pick apart someone else's work who clearly is only offering new ideas that can and should be tested further, whether that be a personal experiment at home, or in a lab.

    Aristo Vojdani defended his work in a response to the article posted on at  Open Original Shared Link and I agree with what he had to say.

    "Open Original Shared LinkMAY 12, 15:45

     

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    knitty kitty

    Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities

    Open Original Shared Link

     

    This article has a section describing the different genotypes of Celiacs and how they react to different gliadin antigens.

     

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    Betsy Bee

    Graves' article is outdated. This is based on an older version of Cyrex Array #4. Dr. Aristo Vojdani has updated Cyrex Array #4 since then. I highly recommend getting Cyrex Array #4 if you are still sick after going gluten free. The newer test spells out which foods are commonly found in patients with celiac disease and with gluten intolerant individuals and it has another section for the foods that really do cross-react. The older test said the whole thing was cross-reactive. Also you don't have to worry about it testing for foods with small amounts of gluten in them. This has been addressed.

    He also has written more recent scientific studies that showed when they look at the data from any patient that has antibodies to Wheat Germ Agglutinin (WGA) the average patient has antibodies to 130-140 other foods. He pretty much coined the terms "molecular mimicry" and "environmental factors".

    Also even though I had taken the earlier version of his test, Cyrex Array #4 did confirm why I wasn't gaining weight after going gluten free. I had antibodies to rice, amaranth, quinoa and other things that gluten free breads are made out of and my reaction was the same as it was to gluten. I finally went from dying at 98 lbs. to 115 and thriving after taking Cyrex Array #4. Very happy with his tests as they saved my life and I think he is ahead of his time.

    Edited by Betsy Bee
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    Guest059483

    I agree! Great research that should be given the light of day as it has helped so many people. I went from 150 looking like death to 180 and feeling great. All my symptoms have gone away completely, and all I had to do was avoid all "gluten free" labeled foods and just eat minimally processed whole foods instead. Cooking was a chore at first, but feeling good and looking good is so worth it.

    That said, some people can function fine with a few small symptoms on a basic gluten free diet, but for those that have real problems that research is critical knowledge.

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    Scott Adams

    Scott Adams was diagnosed with celiac disease in 1994, and, due to the nearly total lack of information available at that time, was forced to become an expert on the disease in order to recover. In 1995 he launched the site that later became Celiac.com to help as many people as possible with celiac disease get diagnosed so they can begin to live happy, healthy gluten-free lives.  He is co-author of the book Cereal Killers, and founder and publisher of the (formerly paper) newsletter Journal of Gluten Sensitivity. In 1998 he founded The Gluten-Free Mall which he sold in 2014. Celiac.com does not sell any products, and is 100% advertiser supported.


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