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  • Jefferson Adams
    Jefferson Adams

    Study Shows Gluten Sensitivity and Celiac Disease Clinically Different

    Reviewed and edited by a celiac disease expert.

    Celiac.com 03/30/2011 - A team of medical researchers set out to compare gut permeability and mucosal immune gene expression in celiac disease and gluten sensitivity.

    The research team included Anna Sapone, Karen M Lammers, Vincenzo Casolaro, Marcella Cammarota, Maria T Giuliano, Mario De Rosa, Rosita Stefanile, Giuseppe Mazzarella, Carlo Tolone, Maria I Russo, Pasquale Esposito, Franca Ferraraccio, Maria Carteni, Gabriele Riegler, Laura de Magistris  and Alessio Fasano.

    People with celiac disease suffer an adverse autoimmune reaction when they consume gluten. People with gluten-sensitivity cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in celiac disease.

    However, for people with gluten intolerance, the overall clinical picture is usually less severe, and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities.

    By examining and comparing mucosal expression of genes associated with intestinal barrier function, along with innate and adaptive immunity the team sought to better understand the similarities and differences between celiac disease and gluten sensitivity.

    For their study, the team enrolled a group of subjects with celiac disease, a group with gluten sensitivity, and a control group of healthy, gluten-tolerant individuals.

    They assessed intestinal permeability using a lactulose and mannitol probe, and collected mucosal biopsy specimens to study the expression of genes involved in barrier function and immunity.

    They found that gluten sensitivity, unlike celiac disease, is not associated with increased intestinal permeability.

    In fact, subjects with gluten sensitivity showed significantly reduced intestinal permeability compared with controls (P = 0.0308). This was accompanied with significantly increased expression of claudin (CLDN) 4 (P = 0.0286).

    Relative to controls, subjects with celiac disease expressed higher levels of adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572), while those with gluten sensitivity showed no higher levels.

    Subjects with gluten intolerance showed increased expression of the innate immunity marker Toll-like receptor (TLR) 2, but subjects with celiac disease showed no such increase (P = 0.0295).

    Finally, subjects with gluten intolerance showed significantly reduced expression of the T-regulatory cell marker FOXP3 relative to controls (P = 0.0325) and celiac subjects (P = 0.0293).

    This study supports the existence of gluten sensitivity and celiac disease as two clinically different gluten-associated disorders.

    The study also supports the characterization of gluten sensitivity as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.

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    Interesting study that proves that there truly is a difference between gluten sensitivity and celiac disease.

    My take away is that both gluten sensitivity and gluten intolerance are mediated by the immune system--just different expressions of the same problem, an immune response to gluten. Are they mediated by the same genetic basis?

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    I do hope this stops those from gluten sensitivity from calling themselves celiacs. As a celiac, it's rather frustrating. These are seemingly 2 different conditions, and there is no benefit to either group by gluten intolerant people considering themselves celiac. You are not celiac. As a celiac, a crumb of gluten will destroy my intestines. This does not happen in gluten intolerance. Now hopefully we can find a way to prevent and cure these conditions (the gluten-free diet is not a cure, it is a treatment, just as insulin does not cure diabetes or nor does an epi pen cure allergies).

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    This article left me wondering whether this means that people who test positive for antibodies to tissue transglutaminase (is that the common blood test for celiac?) have celiac versus a sensitivity. I got the gene test and an antibody test. The gene test showed that I have a pair of genes more commonly associated with gluten sensitivity but my antibody reaction was significant. I've always wondered whether I have celiac or just sensitivity. I suspect that I've got a very permeable gut too as I'm allergic to everything, not just gluten. The permeability could be due to something else though--candida for instance (which is also one of my challenges). Thanks for all the great info. Your articles give me hope for myself and especially for my six year old boy who also has it.

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    While I agree somewhat overall with the team's finding, I also have some major issues with this report:

     

    I have gluten intolerance, and I also have tissue transglutaminase autoantibodies or autoimmune comorbidities. That is, I have low threshold markers of all of the same lab markers that are noted for Celiac disease, just that none of mine put me over the edge of having Celiac disease. The biopsy I had done also showed no Celiac disease, and I had the genetics test taken that showed no propensity for having the Celiac markers. But stating that those with gluten intolerance do not have any of the same lab markers that those with Celiacs do is simply false, as I and my blood work can attest to.

     

    “They found that gluten sensitivity, unlike celiac disease, is not associated with increased intestinal permeability.†This is ONLY true if the only issue you have wrong with your body is gluten intolerance. I also had soy intolerance and a casein allergy when my gluten intolerance was diagnosed, along with a multitude of other intolerances to different foods. I ALSO had severe malabsorption and Leaky Gut, meaning that I had (maybe still have?) very increased intestinal permeability.

     

    Our local gluten intolerance/Celiac group had a researcher from the Celiac research department at the Univ of Chicago come and speak to our group. When I talked to her and mentioned the fact that along with my gluten intolerance not only did I have soy intolerance and casein allergy, but I also had a wide variety of other food intolerances, this researcher then went on to tell me that she does not believe it is possible for a person to have multiple food intolerances and/or allergies to different areas that are not connected or are so very different from each other. And all I could think of was—huh? I and my family are living with multiple food intolerances (we all have gluten intolerance) and all this researcher can say is that she doesn't believe in it? She's not interested in researching to discover WHY our bodies react differently than that of a Celiacs?

     

    Both gluten intolerance and Celiac disease are, at the moment, able to be tolerated with a gluten free diet. As someone else mentioned, it isn't a cure but rather a treatment. Until the real cause of both Celiac and Gluten Intolerance is found, a gluten free diet is the only way to manage symptoms and to prevent more from occurring. I am glad that, finally, scientists/the medical community have discovered that Celiac disease and Gluten Intolerance are two totally different dis-eases with different pathologies. Maybe now we'll finally get someone who is interested in helping those of use with gluten intolerance as well. Although I tend to doubt it, because while ours makes us sick (with a lot of the same issues and problems as Celiac disease), ours doesn't compromise our autoimmune system/give us autoimmune disorders and therefore, we aren't candidates for “drugs.†Well, at least at the moment. Maybe they'll discover after all that they can find a drug to help “cure†us. I suspect, though, that the only cure will be to get rid of wheat/rye/barley from the diet, quit playing around with the germoplasma, and quit playing God with GMOs, chemicals, pesticides, and anything else manmade and not natural. It will be interesting to see what comes about from this study.

     

    Oh! Two things I wanted to mention. 1) While many Celiacs discover they have lactose intolerance, I have been finding out that many people I know who have Gluten Intolerance have either a casein or a whey allergy, along with numerous intolerances to other foods. 2) I also tested positive for severe heavy metal toxicity when I discovered I had gluten intolerance (mine is to the gliadin protein, not the gluten). My question was: why was it so extremely high? I read about the P450 cytochrome--specifically the CYP2C9 gene—and how if you have mutations in this specific cytochrome/gene, your body can't detoxify and metabolize correctly. I was tested, and I have no active alleles and three mutations—meaning my body is unable to detoxify and metabolize at all without help (which I give it with organic food and various supplements, both to support my health/body and to help it detoxify). Once I told my Naturopathic doctor about this specific genetic liver mutation, he told me he'd had 3 more patients after me who had the same liver mutation AND also had gluten/gliadin intolerance.

     

    Perhaps a researcher should look more closely into that.

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    Great article. It affirms that gluten sensitivity is a real issue. So often I get "oh so your celiac"...well not I'm not, but....This also is more evidence to the doctors (like my first doctor) that it there is validity to what my body is doing!

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    What about people who test positive for gluten sensitivity but also have a positive test for and autoimmune reaction to gluten but do not have celiac? Are they celiac, gluten sensitive or something else entirely?

     

    Also, in response to Sarah, what does it matter to you what they call themselves? A crumb of gluten may not be destroying my intestines, but that small crumb gives me all kinds of other symptoms, pain, ataxia, dizziness, vomiting, bloating, and anxiety for an entire week not to mention the gastrointestinal symptoms that occur within twenty minutes of exposure.

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    What about people who test positive for gluten sensitivity but also have a positive test for and autoimmune reaction to gluten but do not have celiac? Are they celiac, gluten sensitive or something else entirely?

     

    Also, in response to Sarah, what does it matter to you what they call themselves? A crumb of gluten may not be destroying my intestines, but that small crumb gives me all kinds of other symptoms, pain, ataxia, dizziness, vomiting, bloating, and anxiety for an entire week not to mention the gastrointestinal symptoms that occur within twenty minutes of exposure.

    Exactly, I have the same problems. Although I had gone on a gluten-free diet per my doctor when I was diagnosed as gluten intolerant, and have been so for 2 years now. I do not know if I am celiac or not, and am unwilling to eat gluten again. All I know is that I cannot tolerate even a crumb of gluten or food with gluten containing substance in it at all.

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    I had both my daughter and I tested for celiac and was told we didn't have it. I had osteoporosis at age 32, IBS, thyroid nodules, autoimmune skin disease and arthritis, and my daughter was born with a Learning Disorder..we've both been dx'd with low vitamin D. I cannot tolerate soy I just found out and I have to take multiple vitamins to treat my symptoms. I am very short, have very short fingers and toes compared to everyone else. I just feel that they are missing something in the diagnosis of gluten disorders. I am way too sick to say there is no damage. And I could not work nor could I get disability since the doctors said nothing is wrong with me.

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    I do hope this stops those from gluten sensitivity from calling themselves celiacs. As a celiac, it's rather frustrating. These are seemingly 2 different conditions, and there is no benefit to either group by gluten intolerant people considering themselves celiac. You are not celiac. As a celiac, a crumb of gluten will destroy my intestines. This does not happen in gluten intolerance. Now hopefully we can find a way to prevent and cure these conditions (the gluten-free diet is not a cure, it is a treatment, just as insulin does not cure diabetes or nor does an epi pen cure allergies).

    A rather strange take from someone who has a condition similar to my own yet implies that NCGS is not worth comment, Being frustrated at this would seem to imply a particular mindset that is not helpful.

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    I do hope this stops those from gluten sensitivity from calling themselves celiacs. As a celiac, it's rather frustrating. These are seemingly 2 different conditions, and there is no benefit to either group by gluten intolerant people considering themselves celiac. You are not celiac. As a celiac, a crumb of gluten will destroy my intestines. This does not happen in gluten intolerance. Now hopefully we can find a way to prevent and cure these conditions (the gluten-free diet is not a cure, it is a treatment, just as insulin does not cure diabetes or nor does an epi pen cure allergies).

    I understand. My son has severe milk allergies and people are constantly calling him lactose intolerant. I'm like, 'No, he is allergic. He can die from it."

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  • About Me

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

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