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

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.

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 CD 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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7 Responses:

 
Jenice Yoder
Rating: ratingfullratingfullratingfullratingfullratingfull Unrated
said this on
10 Sep 2008 7:32:57 AM PST
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.

 
krista
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said this on
11 Sep 2008 4:42:15 PM PST
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.

 
Jacqui
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said this on
12 Sep 2008 8:37:38 PM PST
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.).

 
MichaelG
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said this on
03 Oct 2008 9:21:14 AM PST
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.

 
Naomi Kyle
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said this on
29 Mar 2009 2:58:03 PM PST
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.

 
Brendan

said this on
13 Feb 2015 8:44:34 AM PST
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.)

 
Nevrdun
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said this on
23 Feb 2012 11:49:02 AM PST
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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