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Neurological Gluten Sensitivity Symptoms Linked to TG6 Autoantibodies

Celiac.com 11/01/2012 - Although most instances of gluten sensitivity manifest as a chronic, autoimmune disorder of the small intestine (celiac disease), around 10% of gluten sensitive patients suffer neurological symptoms. Usually these neurological symptoms accompany the more common intestinal issues, but some patients exhibit neurological symptoms exclusively. For this reason, it is thought that gluten-related symptoms in different parts of the body could be the result of autoimmune reactions to different members of the transglutaminase gene family. A recent lab study suggests that neurological gluten-related symptoms could be the result of an immune reaction to a particular neuronal enzyme known as TG6, and that this reaction occurs separate from other autoimmune reactions to gluten.

Photo: CC--GE HealthcareSera were collected from 6 groups: 20 newly diagnosed celiac disease patients (pre gluten-free diet) with no neurological symptoms, 34 gluten ataxia patients who tested positive for anti-gliadin antibodies, 17 peripheral idiopathic neuropathy patients, also positive for anti-gliadin antibodies, a control group of 18 genetic (non-gluten related) ataxia patients or individuals with clear family history of ataxia, a second control group of 14 patients with various immune-mediated but gluten-unrelated diseases and a third control group of 19 healthy individuals. Sera were tested through a series of protein analyses and enzyme-linked immunosorbent assays.

In the celiac disease group, 18 of 20 patients tested positive for the TG2 autoantibody, with the remaining two testing postive for the TG3 or TG6 autoantibodies. 55% of celiac disease patients had multiple transglutaminase autoantibodies: 45% of all celiac disease patients had antibodies for both TG2 and TG3, 45% had antibodies for both TG2 and TG6, and 35% had antibodies for TG2, TG3 and TG6.

Gluten ataxia patients were separated into two groups: those with intestinal symptoms (group GAE), and those without (group GAo). TG2 autoantibodies correlated well with intestinal symptoms: 12 of 15 in the GAE group tested positive for TG2 autoantibodies, while only 1 of 19 in the GAo group tested positive for them. TG3 autoantibody results were similar: group GAE results were comparable to the celiac disease group, while group GAo was no different from the control groups. In contrast, both gluten ataxia groups had similar results for TG6 autoantibodies. Overall prevalence of TG6 autoantibodies in the gluten ataxia group was 62%, compared to 45% in the celiac disease group.

Inhibition studies showed that in group GAE (gluten ataxia with intestinal symptoms), autoantibodies reacted separately from one another, with TG2 and TG6 autoantibodies reacting independently of one another to their respective TG isozymes. This, along with the fact that some patients tested positive exclusively for TG6 would suggest that intestinal and neurological gluten-related symptoms are caused by separate immune reactions to different TG isozymes (TG2 and TG6, respectively). This is further supported by postmorten analysis of a gluten ataxia patient without intestinal symptoms, where TG6 deposits were found in the brain (TG6 could not be detected in a normal cerebellum).

The findings of this study suggest that with more research, doctors may have another diagnostic tool in the form of TG6 autoantibody tests. This would help determine which patients with gluten sensitivity might be most at risk for developing neurological symptoms.

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4 Responses:

 
stu
Rating: ratingfullratingfullratingfullratingfullratingfull Unrated
said this on
07 Nov 2012 12:41:28 PM PST
This is excellent news, however, the biggest obstruction will remain firmly fixed in place, I fear - That of actually convincing your PCP that you might have a gluten problem to begin with.

 
Beth kaiser
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said this on
07 Apr 2013 2:36:58 PM PST
I lived for 50 years with all the wrong diagnoses!!! I thought I was going to die, I was beyond ill... Now that I am an auto immune nightmare from head to toe, the doctors are finally taking me and my plethora of illnesses seriously!!! Never give up the quest for better quality of life!!! The medical community puts its pants on one leg at a time, just like the rest of us!!! In my case, they were dead wrong until I started reading, and, thinking outside the traditional Medical Box!!!I demanded the celiac testing even though my doctors said I was way off base... Oh REALLY?! Once I was told I have had severe celiac from birth!!! I went to work in an attempt to help my Aching, Arthritic, Thyroid Diseased, Fibromayalgia Ridden, Brain Fogged, Rash Infested, 25 Trips to the bathroom, Inflamed body!!! Keep fighting the good fight!!! Never give up!!! Things can get a bit better, one hour at a time!!! The medical research will catch up with us all!!! Patience and perseverance: my mantra!!! Keep reading!!! Never ever give up!!!! Be well.

 
Coloradosue
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said this on
10 Nov 2012 11:43:32 PM PST
My brother exhibited neurological symptoms years before self diagnosis of celiac disease by going on a gluten free diet. He previously was diagnosed with MS, but a recent physical showed no indication of the disease. So then what is the cause of his neurological deficits? I suspect it is celiac disease. I am now exhibiting some problems, which only become worse after anything requiring physical work. And what does fibromyalgia contribute to this equation? For me, things are getting worse. I hope that these researchers are able to find the answers to these questions, if not in my lifetime, for my daughter and grandsons (and other members of my family) who were recently diagnosed with celiac disease. What an awful legacy to leave them.

 
Diana
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said this on
26 Sep 2013 4:18:15 AM PST
Coloradosue,

Fibromyalgia is simply severe inflammation which gluten gives you in spades if you are allergic. Like Beth, I've been allergic since birth and was 46 before being diagnosed.
I was blessed to find a homeopathic doctor who knew what to do.




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