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    Tg6 Antibody Plays a Key Role in Celiac Disease-Related Neurological Disorders


    Jefferson Adams

    Celiac.com 09/02/2008 - Thanks to a team of  researchers based in Great Britain, doctors may soon have a powerful new diagnostic tool to help them in their efforts to combat the damage caused by celiac disease. Their new discovery concerns people with celiac disease who may also develop neurological disorders.


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    The research team was made up of Marios Hadjivassiliou, MD, Pascale Aeschlimann, BSc, Alexander Strigun, MSc, David Sanders, MD, Nicola Woodroofe, PhD, and Daniel Aeschlimann, PhD.  The team recently investigated the nature of gluten sensitivity by isolating a unique neuronal transglutaminase enzyme and examining whether it is the focus of the immune response in celiac patients with neurological dysfunction.

    About one in ten people with celiac disease also suffer from associated neurological disorders, mainly from a condition involving the cerebellum called gluten ataxia, and another involving the peripheral nerves called gluten neuropathy. For many people celiacs with gluten ataxia, their neurological problems are their sole symptom. Only about 1 out of 3 people with gluten ataxia and celiac disease will show classic intestinal damage when given a biopsy. This can make proper diagnosis difficult for them. Also, there’s presently no reliable way to predict which people with gluten intolerance might develop neurological problems.

    Most people familiar with celiac disease know that gastrointestinal discomfort is one of the most common symptoms. The antibody most commonly associated with such discomfort is called anti-transglutaminase 2 IgA. This is one of the main antibodies that doctors commonly look for when evaluating possible cases of celiac disease. Anti-TG2 antibodies are pretty much exclusive to people with celiac disease, and are associated with both untreated clinically symptomatic celiac disease, and with the latent form of the disease. This makes the presence of anti-TG2 antibodies an excellent diagnostic indicator of celiac disease.

    Anti-TG2, however, may not be the best indicator in every case of celiac disease. One example is in cases of dermatitis herpetiformis, which is an external skin reaction to gluten. Most people with dermatitis herpetiformis have a persistent itchy skin rash, and while the majority of cases show intestinal damage with a biopsy, patients rarely experience intestinal discomfort associated with classic celiac disease.1 There is also reliable data that point to a role that anti-TG3 plays in cases of dermatitis herpetiformis.2 This indicates that the nature of a given individual’s immune response may determine how celiac disease manifests itself within that individual.

    That hypothesis seems to be born out by the research team’s discovery that another antibody, called anti-transglutaminase 6 IgG and IgA response is widespread in gluten ataxia, completely outside of any intestinal symptoms. These antibodies are not found in healthy control patients or in patients with neurological conditions that had clear genetic causes. Both groups showed no anti-TG6 in their blood samples.

    The research team took blood samples from 20 patients with newly diagnosed celiac disease before the patients began a gluten-free diet. The team confirmed the presence of celiac disease with duodenal biopsy and made sure the patients had no patients had no evidence of neurological problems.

    The team then took blood samples from 34 patients with Gluten Ataxia, which they defined as otherwise sporadic idiopathic ataxia with positive IgG and/or IgA anti-gliadin antibodies.

    The also took samples from another17 patients with peripheral idiopathic neuropathy (PN) who tested positive for anti-gliadin antibodies. These 17 patients tested negative for anti-MAG and anti-GM1 and had no evidence of intestinal damage on biopsy.

    The team used three separate control groups. The first was a group with genetic ataxia, which included 18 patients with ataxia that was genetic in nature, or with a clear family history of autosomal dominant ataxia. The second control group of 14 patients included cases of diseases that were immune-mediated, but not tied to gluten-sensitivity (such as vasculitis, viral cerebellitis, paraneoplastic ataxia, GAD ataxia). Lastly, the team used blood samples from 19 healthy individuals as another control group.

    The research team used recombinant human transglutaminases to develop ELISA and inhibition assays with which they measured blood samples of patients with gluten sensitive gastrointestinal and neurological disorders, along with several control groups that included unrelated inherited or immune conditions, for the presence and specificity of autoantibodies.

    The team found that the blood samples of patients with celiac disease and gluten ataxia contain IgA and IgG class antibodies to TG6 that are not present in the healthy control patients or in patients with neurological conditions that had clear genetic causes.

    At present, doctors test for celiac disease by checking the HLA type, and looking for the presence of anti-gliadin and anti-transglutaminase 2 antibodies. The results of this study indicate that the presence of anti-transglutaminase 6 can help to pinpoint patients with gluten sensitivity that may be at risk of developing neurological disease.

    Forthcoming: Annals of Neurology

    Footnotes:
    1. Marks J, Shuster S, Watson AJ. Small bowel changes in dermatitis herpetiformis. Lancet 1966; 2:1280-1282.

    2. Sárdy M, Kárpáti S, Merkl B, Paulsson M, and Smyth N. Epidermal transglutaminase (TGase3) is the autoantigen of Dermatitis Herpetiformis. J Exp Med 2002; 195:747-757.

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    Guest Jenice Yoder

    Posted

    I have long wondered if my mother's Parkinson's Disease and her sometimes questionable diagnosis of celiac disease (manifested in dermatitis herpetiformis) were related.

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    I am glad to see research being done in this area. I wonder if this same marker shows with the folks whose symptoms are largely 'mood' oriented. If so it would be a very beneficial test to use before putting people on psychotropics.

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    I found this very interesting but would like more info. I have 2 and 6 genes, my labs were barely positive and my biopsy was 3+ out of 4 and I have every neurological symptom but after 7 neurologists I still have no diagnoses. Only one neurologist said Celiac Disease can cause neurological symptoms.

    I also e-mailed Dr. H a year or so ago and he originally told me that I would be better after a year of eating gluten free. It is now 2 1/2 yrs. My symptoms are less intense than 3 years ago (it took 6 months to finally be diagnosed after waking up unable to walk or stay awake, but had symptoms for ~12 yrs.).

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    Guest MichaelG

    Posted

    Very interesting article. One doctor I know suggested that a friend of mine that is celiac with a severe neuropathy problem take Alpha Lipoic Acid and Inositol powder. I know that the ALA is good for other types of neuropathy according to PubMed and the British Journal of Medicine. I guess only time will tell.

    I do know that he is having a very difficult time figuring out how to live gluten free.

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    Guest Naomi Kyle

    Posted

    Good information. My daughter age 6 was diagnosed with an extreme case of ataxia causing her to be physically delayed. Her neurologist felt this is in response to her reaction to gluten. Apparently her anti-gliadin levels are triple the range for her age. How I understand the extra antibodies are attacking her cerebellum causing her extreme ataxia. We have been on a gluten free diet for three years now and have only witnessed a mild improvement. I hope to continue to learn more of how to reverse this issue.

    Thank you for the information.

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    Guest Nevrdun

    Posted

    So where can you get this test done? Is it available in the US.. need more info ..this is only half the information and you had to know everyone would want to know that!

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    Guest Brendan

    Posted

    Good information. My daughter age 6 was diagnosed with an extreme case of ataxia causing her to be physically delayed. Her neurologist felt this is in response to her reaction to gluten. Apparently her anti-gliadin levels are triple the range for her age. How I understand the extra antibodies are attacking her cerebellum causing her extreme ataxia. We have been on a gluten free diet for three years now and have only witnessed a mild improvement. I hope to continue to learn more of how to reverse this issue.

    Thank you for the information.

    I would love to find out how your daughter has progressed.

    My wife (much older) has "idiopathic" peripheral neuropathy but recently underwent tests associated with gluten intolerance. The results came back positive for Transglutaminase-6 IgG which might be the first step in halting the neurological problem, which is beginning to ruin her life (lost sensation in lower legs and feet - feels unsafe in some situations. She used to be very able-footed, hill walking etc.)

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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  • Related Articles

    Jefferson Adams
    Celiac.com 06/08/2007 -The results of a study recently published in the Alimentary Pharmacology & Therapeutics indicates that patients with celiac disease face a significant risk of polyneuropathy.
    Faced with inconclusive evidence of past studies linking celiac disease to various neurological conditions, doctors J. F. Ludvigsson, T. Olsson, A. Akbom, and S.M. Montgomery, set out to provide more conclusive evidence regarding the association between celiac disease and several neurological diseases. They used Cox regression to examine the risk of neurological disorders in 14,000 people who were diagnosed with celiac disease between 1964 and 2003. These patients were compared with 70,000 reference individuals matched for age, sex, calendar year and county.
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    The actual study results are as follows:
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    Because the connections between celiac disease and polyneuropathy indicate shared risks the doctors suggest that people with polyneuropathy undergo regular screening for celiac disease.
    health writer who lives in San Francisco and is a frequent author of articles for Celiac.com.

    Jefferson Adams
    Celiac.com 02/09/2009 - Doctors are recommending simple, low-cost blood tests to screen for celiac disease in patients who have Restless Leg Syndrome (RLS) with low serum ferritin, but who otherwise show no clear cause for iron deficiency.
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    Source: Sleep Med. 2009 Jan 10. PMID: 19138881

    Jefferson Adams
    Celiac.com 08/13/2009 - In the latest issue of the journal Medical Hypotheses, Dr. Rodney Philip Kinvig Ford of the Children’s Gastroenterology and Allergy Clinic in Christchurch, New Zealand, offers up a compelling hypothesis regarding celiac disease and gluten sensitivity, which asserts that the broad array of associated symptoms are more fully explained using a neurological perspective, than using a digestive/nutritional perspective.
    For Dr. Ford, the idea that celiac disease is exclusively an auto-immune condition, and that nutritional mal-absorption is the main cause of related problems, is simply not borne out by the body of clinical data.
    Dr. Ford accepts that celiac disease may itself be largely an auto-immune disorder. However, he believes that the broad array of problems associated with gluten intolerance are best explained by looking at the neurological aspects of intolerance to gluten, indeed, treating it as a neurological condition.
    That's because gluten intolerance can affect up to up to 10% of the population, and that intolerance to gluten has largely neurological manifestations. That is, up to 10% of the population tests positive for elevated antibodies for gluten, even with no bowel damage.
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    Under Dr. Ford hypothesis, if gluten is the assumed cause of harm, then exposure to gluten in sensitive individuals may cause neurological harm through a combination of cross-reacting antibodies, immune complex disease and direct toxicity.
    It's certainly true that a number of celiac patients experience neurological symptoms, often associated with autonomic nervous system malfunction.
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    Hypothesis: Gluten causes symptoms, in both celiac disease and non-celiac gluten-sensitivity, by its adverse actions on the nervous system.
    Many celiac patients experience neurological symptoms, frequently associated with malfunction of the autonomic nervous system. These neurological symptoms can present in celiac patients who are well nourished. The crucial point, however, is that gluten-sensitivity can also be associated with neurological symptoms in patients who do not have any mucosal gut damage (that is, without celiac disease).
    Gluten can cause neurological harm through a combination of cross-reacting antibodies, immune complex disease and direct toxicity. These nervous system affects include: dis-regulation of the autonomic nervous system, cerebella ataxia, hypotonia, developmental delay, learning disorders, depression, migraine, and headache.
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    ( Possible celiac was revealed in 48 patients (6.6%), who had elevated tTG antibodies, but normal gut histology: 75% of these patients reported improvement on a gluten-free diet.
    © Not-celiacs, n=644 (89.1%), with normal tTG antibodies and no evidence of gut damage: 53% reported improvement gluten-free.
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    The three groups all shared similar clinical features. In the respective groups, 71%, 65%, and 51% of patients reported behavior issues, such as tiredness, lethargy, irritability, sleep disturbance, while 16%, 15%, and 24% reported gastric reflux. Dr. Ford believes these symptoms are likely to be neurologically driven by gluten-sensitivity.
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    These patients are likely candidates for what he calls 'gluten syndrome.' These children can likely be spotted via screening for high IgG-gliadin levels.
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    Medical Hypotheses 73 (2009) 438–440


    Jefferson Adams
    Celiac.com 01/19/2010 - A new study says that migraines and carpal tunnel syndrome may point to celiac disease. Moreover, 35% of people with celiac disease report a history of depression, personality changes, or psychosis. Others commonly suffer from neurological issues that are not improved with a gluten-free diet.
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    Source: Mov Disord. 2009;24:2358-2362.


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    Source:
    PLoS Med. 2018 Feb; 15(2): e1002507. doi:  10.1371/journal.pmed.1002507

    Jefferson Adams
    Celiac.com 07/17/2018 - What can fat soluble vitamin levels in newly diagnosed children tell us about celiac disease? A team of researchers recently assessed fat soluble vitamin levels in children diagnosed with newly celiac disease to determine whether vitamin levels needed to be assessed routinely in these patients during diagnosis.
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    Source:
    BMC Pediatrics

    Jefferson Adams
    Celiac.com 07/16/2018 - Did weak public oversight leave Arizonans ripe for Theranos’ faulty blood tests scam? Scandal-plagued blood-testing company Theranos deceived Arizona officials and patients by selling unproven, unreliable products that produced faulty medical results, according to a new book by Wall Street Journal reporter, whose in-depth, comprehensive investigation of the company uncovered deceit, abuse, and potential fraud.
    Moreover, Arizona government officials facilitated the deception by providing weak regulatory oversight that essentially left patients as guinea pigs, said the book’s author, investigative reporter John Carreyrou. 
    In the newly released "Bad Blood: Secrets and Lies in a Silicon Valley Startup," Carreyrou documents how Theranos and its upstart founder, Elizabeth Holmes, used overblown marketing claims and questionable sales tactics to push faulty products that resulted in consistently faulty blood tests results. Flawed results included tests for celiac disease and numerous other serious, and potentially life-threatening, conditions.
    According to Carreyrou, Theranos’ lies and deceit made Arizonans into guinea pigs in what amounted to a "big, unauthorized medical experiment.” Even though founder Elizabeth Holmes and Theranos duped numerous people, including seemingly savvy investors, Carreyrou points out that there were public facts available to elected officials back then, like a complete lack of clinical data on the company's testing and no approvals from the Food and Drug Administration for any of its tests.
    SEC recently charged the now disgraced Holmes with what it called a 'years-long fraud.’ The company’s value has plummeted, and it is now nearly worthless, and facing dozens, and possibly hundreds of lawsuits from angry investors. Meantime, Theranos will pay Arizona consumers $4.65 million under a consumer-fraud settlement Arizona Attorney General Mark Brnovich negotiated with the embattled blood-testing company.
    Both investors and Arizona officials, “could have picked up on those things or asked more questions or kicked the tires more," Carreyrou said. Unlike other states, such as New York, Arizona lacks robust laboratory oversight that would likely have prevented Theranos from operating in those places, he added.
    Stay tuned for more new on how the Theranos fraud story plays out.
    Read more at azcentral.com.