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    Jefferson Adams

    Study Shows Gluten Sensitivity and Celiac Disease Clinically Different

    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 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 biology, anatomy, medicine, science, and advanced research, and scientific methods. He previously served as 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.

  • Related Articles

    Jefferson Adams
    New Study Shows Celiac Disease on the Rise, Striking Later in Life
    Celiac.com 10/26/2010 - A recent study shows that, since 1974, the rate of celiac disease has doubled every fifteen years, and that celiac rates increase as people grow older, with many developing the disease in their 50s or 60s.
    The Center for Celiac Research led the study, which looked at 3,511 volunteers who submitted blood samples in 1974 and 1989, along with updates every two to three years until 2007.
    Because researchers in the study surveyed the same people over time, says Mayo Clinic gastroenterologist Dr. Joseph Murray, the study adds weight to the concept that celiac disease can emerge at any age.
    The study results also echo those of a 2008 Finnish study that found that elderly people had rates of celiac disease nearly two and a half times higher than the general population.
    The fact that celiac disease seems to be increasing among older age groups is significant because, if someone can be gluten-tolerant for 40 or 50 years before developing celiac disease, environmental factors may outweigh genetic causes for the disease, says Alessio Fasano, director of the Center for Celiac Research.
    Fasano says that other unknown environmental changes and changes in "the composition of bacteria in our guts" may be causing gluten autoimmunity to present itself later in life.
    Although researchers have identified specific genetic markers for the development of celiac disease, the exact way in which people lose tolerance to gluten remains unknown.
    However, it's important to understand that even people who have the genetic markers in question are not fated to develop an autoimmune disease, says Fasano. That's because recent study shows "that environmental factors cause an individual's immune system to lose tolerance to gluten, given the fact that genetics was not a factor in our study since we followed the same individuals over time," he says.
    If environmental factors do play a role in celiac disease, then it will be interesting to see if certain areas and regions have high celiac rates that are not due to genetic factors.
    More importantly, the research team notes that by identifying the environmental factors behind celiac disease, researchers may lead to better treatment and possible prevention of celiac disease and other autoimmune disorders, including type 1 diabetes, rheumatoid arthritis and multiple sclerosis.

    SOURCE:
    Annals of Medicine: October 2010, Vol. 42, No. 7 , Pages 530-538
    doi:10.3109/07853890.2010.514285



    Jefferson Adams
    Study Shows Gluten Intolerance Without Celiac Disease
    Celiac.com 02/14/2011 - In what may seem for some like an obvious finding, a team of Australian researchers has shown that people can suffer gluten intolerance without having celiac disease. Their study is published in The American Journal of Gastroenterology.
    I say obvious, because many in the celiac and surrounding community have long understood and accepted the concept of gluten-intolerance as distinct from celiac disease. Surprisingly, there has been very little scientific research to establish the existence of gluten-intolerance as distinct from celiac disease. That is changing, and the recent Australian study offers some support for gluten-intolerance as distinct from celiac disease.
    For their study, a team of researchers led by Peter Gibson, professor of medicine at Eastern Health Clinical School at Monash University in Australia, recruited 34 people with irritable bowel syndrome, but who were clinically proven to be free of celiac disease. All participants had previously benefited from a gluten-free diet.
    The 34 volunteers were all fed bread and muffins, half of which contained gluten, half of which were gluten-free. Nearly 70 per cent of the volunteers who ate the gluten reported pain, bloating, toilet problems and extreme tiredness.
    ''Gluten is indeed a trigger of gut symptoms and tiredness,'' the researchers concluded. Professor Gibson said: ''These symptoms have a big impact on quality of life. But conservative medicine has not been so good at dealing with this because we haven't had any evidence.''
    A number of the volunteers had sought help from alternative health practitioners, a fact that impaired recruitment of volunteers, as many of these folks had adopted a gluten-free diet without proving or disproving celiac disease via colonoscopy and biopsy.
    It was important for the team to exclude celiac disease for several reasons, including the fact that although it was safe to use gluten to test people who may have an intolerance, it could harm people with celiac disease.
    "If you go back on gluten while you have celiac disease - even if you only eat a few pieces of bread - you will damage your body and undo many months of healing," Professor Gibson said.
    For that reason, and also to prove gluten intolerance alone was the symptom cause, the team recruited people  clinically proven to be free of celiac disease, and who were already on gluten-free diets.
    For those patients with irritable bowel syndrome, excluding celiac disease, who were symptomatically controlled on a gluten-free diet, the team crafted a double-blind, randomized, placebo-controlled re-challenge trial.
    Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. The team evaluated symptoms using a visual analog scale and markers of intestinal inflammation, injury, and immune activation monitoring.
    A total of 4 men and 30 women between the ages of 29–59-years old completed the study as per protocol. Overall, 56% showed human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high.
    Of 19 patients (68%) in the gluten-consuming group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation).
    On a visual analog scale, patients were significantly worse within one week of consuming gluten for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001).
    In no cases did gluten-consumption trigger anti-gliadin antibodies. Moreover, there where were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with the DQ2/DQ8 and those without.
    Gibson calls the general lack of research into gluten intolerance "almost unbelievable." He plans to now investigate the prevalence of non-celiac gluten intolerance, why it occurs and whether low levels of gluten can be eaten safely.

    Source:

    American Journal of Gastroenterology: 11 January 2011. doi: 10.1038/ajg.2010.487

    Jefferson Adams
    Celiac.com 08/01/2011 - Over the last two decades, there has been a marked increase in the prevalence of celiac disease, especially the sub-clinical celiac disease forms and non-celiac gluten sensitivity. Most people with celiac disease now present atypical or non-classical symptoms.
    However, even with improved evaluation methods, clinicians may often face variable histological and clinical presentations of celiac disease, and they may be confused by diagnostic models in the current guidelines.
    A team of researchers recently set out to reassess sub-clinical celiac disease and gluten sensitivity. The study team included Mohammad Rostami Nejad, Sabine Hogg- Kollars, Sauid Ishaq, Kamran Rostami
    They are affiliated variously with the Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran, School of Immunity and Infection, University of Birmingham, and the Dudley Group of Hospital NHS Foundation Trust, both in the UK.
    Improved celiac evaluation methods, and the discovery such conditions as non-celiac gluten sensitivity have them recommending that clinicians use the term 'sub-clinical' in place of  'silent,' and 'atypical' in place of 'potential/latent,' as a way to better understand clinical atypical celiac disease. 
    Although terminologies like 'latent,' 'silent' and 'potential' do reflect certain observable aspects of clinical and pathological celiac disease, they also cause some confusion between clinicians and patients, in part because the definitions are still somewhat vague and subjective.
    The researchers point out that 'silent' celiac disease is not actually silent after all. Rather, patients show signs of celiac disease with no significant symptoms. Meanwhile, the terms 'potential' and 'latent' are defined differently across numerous studies.
    The researchers point out the widening spectrum of gluten related disorders, and note that these common systemic disorders have numerous causes with a variety of symptoms and complications inside and outside the small bowel.
    They conclude that the body of evidence supports decreasing the treatment threshold in people with atypical celiac disease and gluten sensitivity. Since long-term complications of sub-clinical celiac disease remain unknown, they say, it is appropriate to diagnose such patients as early as possible, and to treat them with a gluten-free diet.
    Source:

    Gastroenterology and Hepatology From Bed to Bench. 2011;4(3): 102-108

    Jefferson Adams
    Blood Tests Different in Patients with Gluten Sensitivity Than in Those with Celiac Disease
    Celiac.com 12/03/2012 - Gluten sensitivity has recently been added to the spectrum of gluten-related disorders, but precise diagnostic markers do not yet exist. A research team recently set out to understand the blood test pattern of gluten sensitivity, and to compare it with the blood test pattern seen in celiac disease.
    The researchers included U. Volta, F. Tovoli, R. Cicola, C. Parisi, A. Fabbri, M. Piscaglia, E. Fiorini, G. Caio, of the Department of Clinical Medicine at University of Bologna's St. Orsola-Malpighi Hospital in Bologna, Italy.
    For their study, the researchers looked at blood samples from 78 patients with gluten-sensitivity and 80 patients with celiac disease. They assessed levels of immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA).
    They found positive readings for IgG AGA in 56.4% of patients with gluten-sensitivity, and in 81.2% of patients with celiac disease. Antibody levels for both groups were in the high range.
    They found IgA AGA in 7.7% of patients with gluten-sensitivity, and in 75% of patients with celiac disease, which shows lower enzyme-linked immunosorbent assay activities in gluten-sensitivity patients than in patients with celiac disease.
    Only 1 of the 78 patients with gluten-sensitivity tested positive for IgG DGP-AGA, which was found in nearly 90% of patients with celiac disease.
    All patients with gluten-sensitivity tested negative for IgA tTGA and IgA EmA, while 98.7% of patients with celiac disease tested positive for IgA tTGA, and 95% were positive for IgA EmA.
    Patients with gluten-sensitivity presented a variety of intestinal and extra-intestinal symptoms, including abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia. Small intestinal mucosa for these patients was either normal or only mildly abnormal.
    The data from these blood tests show that more than half of patients with gluten sensitivity will test positive for IgG AGA, and a small number will test positive for IgA AGA, but none will show positive results for EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.
    Source:
    J Clin Gastroenterol. 2012 Sep;46(8):680-5.

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