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Study Shows Gluten Sensitivity and Celiac Disease Clinically Different

N new study on gluten sensitivity and celiac disease. Photo: CC-Ell Brown 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.

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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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18 Responses:

Jay K.
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said this on
30 Mar 2011 2:22:24 PM PST
Interesting study that proves that there truly is a difference between gluten sensitivity and celiac disease.

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said this on
04 Apr 2011 10:04:28 AM PST
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?

Susan Lederer
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said this on
04 Apr 2011 6:03:08 AM PST
Not enough details but a worthwhile study.

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said this on
04 Apr 2011 3:09:38 PM PST
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 GF 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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said this on
29 Aug 2011 6:51:37 AM PST
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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said this on
01 Nov 2011 4:58:24 PM PST
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."

Jim Ford
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said this on
09 Dec 2011 12:19:39 PM PST
My son tests negative for celiac disease but develops extreme psychosis from gluten (has very high anti-gliadin antibodies). In CD gluten causes the immune system to attack the lining of the gut. GS can affect many organ systems, especially the nervous system and is linked to ataxia, epilepsy, schizophrenia, ADHD, autism and very likely MS. These can be just as severe and in some cases as deadly as CD.

Janet Brewer
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said this on
17 Jan 2013 4:36:31 PM PST
WHOA Girl, you seem very angry Sarah, you sound pretty worked up over someone with gluten intolerance saying they have celiac disease. Too many other things in life a lot worse than that! Settle down!

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said this on
04 Apr 2011 8:35:58 PM PST
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.

Ann C.
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said this on
05 Apr 2011 10:25:36 AM PST
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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said this on
31 May 2012 6:38:01 PM PST
I would really like to hear more of what you have to say. I am just beginning all of this and you seem to have a lot of knowledge.

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said this on
05 Apr 2011 1:54:12 PM PST
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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said this on
07 Apr 2011 9:19:12 AM PST
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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said this on
04 Jun 2011 2:03:17 PM PST
Exactly, I have the same problems. Although I had gone on a GF 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.

Cheryl Keeney
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said this on
24 Jul 2011 1:41:24 PM PST
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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said this on
13 May 2012 12:34:32 AM PST
Would be interesting to see how many people have heart problems with their gluten sensitivity? I have arrhythmia within half an hour of having small quantities of gluten. Large quantities, as well as rice, send me into tachycardia...along with all the other gut issues etc.

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said this on
13 Aug 2012 4:03:01 AM PST
I suspect that I am celiac. I am short, skinny, and recently have been suffering from strange bowl movements like steatorrhea, constipation and diarrhea, as well as nausea. I want to do a biopsy but I am somewhat lazy and pessimistic about the test. I eat a lot but I can't gain any weight. I guess that my villi can't absorb the nutrients. I ask God to help me find my disease so that I start my gluten free diet. I can't try a gluten few diet because my mom always cooks wheat food and she gets really angry when I don't eat.

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said this on
18 Aug 2015 12:44:20 PM PST
Because the diagnosis for celiac is a biopsy and some of us never get a biopsy- and we are gluten intolerant- how do we know if we are celiacs or not? I tested negative for the antigen test and therefore could not be given a biopsy- but I have the DNA markers for celiac and have elected to go gluten-free and get sick if I accidentally eat anything containing gluten. I would be labelled "Gluten Intolerant," but now that I am on a gluten-free diet and not willing to go back to gluten- how would I know I am not a celiac- a latent celiac or a silent celiac?? Is it possible that there is a range of symptoms for anyone who cannot tolerate gluten in their diet? Maybe at one end they get the "Celiac" label and at the other they get "Gluten Intolerant" label for the same problem? Certainly, I need better information and the doctors need to have better information. There needs to be more studies.

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