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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.

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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 PDT
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 PDT
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 PDT
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 PDT
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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Dang! If I lived that close to Chicago, I would definitely go to the University of Chicago's celiac center even just to hang out with some celiacs or celiac-savvy folk! (Maybe visit Aunt Mary too....) Consider a second opinion. Some people spend more on their Friday night bar tab instead of paying for a second opinion (cash) if they went out-of-network (insurance). Your current GI must suspect something (e.g. parasite). Maybe he is hoping it will resolve on its own (frankly sometime this approach works), but that side pain for over a year is not normal. Keep advocating. ?

Cycling Lady, LMAO at IBeStumped! So true. Yes, he is trying the band aid approach it seems. That's probably the most frustrating thing of all. So yesterday I get a call back from his office and they say to stop taking the Viberzi and switch back to Imodium! I reminded them that Imodium didn't work, I had already used it 8 days with no changes. His assistant informed me that that is all he can recommend at this time until he sees me at my next appointment which is 5/24! I live near Chicago and I am about to make an appointment to go to the University of Chicago hospital which is the top celiac research hospital in the country. Hopefully they can give me better answers.

7Hi jen and welcome No-one can diagnose remotely via nterwe posts but if there was such a game as celiac / gluten sensitive bingo, I would be calling 'House!' having read your account above... Lots of things fit the pattern as I'm sure your lurking has revealed. It's a tricky condition to diagnose however so you may have a little wait before you join the coolest club in town and get your funky celiac membership card For now it's really important that you stay on gluten. Keep eating it as accurate testing requires it. Ask your doctor to check the boxes for celiac testing alongside your liver blood tests. There should be enough in your history to get this without hassle but if they're reluctant INSIST and don't be afraid to assert your reasonable suspicion and wish to clarify and exclude. A good liver specialis will be aware of the possible links so you should be ok. If not gt second opinion. Ask for a full celiac panel as there are variety of tests. Find further info here There's a lot to take in, but be positive, I think you are on the right track and if so, you could soon be feeling better than you ever thought possible!

Hello, I am in a job that I travel every 3rd week...It gets challenging becuase many times I am doing audits of warehouses and they dont even have a cafeteria. I usually bring gluten-free protein bars as a back up if I have to miss a meal and then eat when I get back to the hotel. Just a suggestion because they certainly fill me up....Have a safe trip...Kelly

Hello all, I'm a new member here but have lurked for a while. I'm looking for some advice regarding my medical history, possible symptoms of celiac and next steps. General info: female, low level smoker, drink alcohol, aged 32. I started having bad gastro issues when I was around 17. Since then I've consistently suffered from chronic diarrhoea, frequent discomfort in the tummy area, feelings of dehydration despite drinking at least eight glasses a day and frequent fatigue for no real reason. In 2008/9 I visited the doctor as my diarrhoea was having an effect on my studies at the time. The doctor tested me for allergies; eggs, fish, gluten and lactose and did a "standard" blood test. Everything came back fine except my liver results, which were elevated to double (I did not the see the results for myself so can't say which enzymes etc). I was told to drink less and take Imodium. The doctor implied that perhaps I was stressed and / or anxious and, still being young plus a student who regularly went out drinking, I accepted this advice and carried on with my life. I would here add that I am not an unusually stressed person - in fact, learning to deal with my unpredictable bowels has forced me to be quite a laid-back person! Fast forward to 2016. I had been living with my partner for two years by this point who had noticed my bowel habits and informed me that this was definitely not normal. He encouraged me to try out a gluten free diet since I was apprehensive about visiting a doctor only to be fobbed off with Imodium again. I did the diet as strictly as a newbie can for around two months before we set off travelling. During the diet I noticed that after a couple of weeks of extreme tiredness I felt quite a lot better - I kept a food journal at the time which showed that I almost immediately had diarrhoea once after eating an ice-cream, i felt bloated and unwell after an attempt to make oat muffins (maybe i didn't cook them very well though!) and I felt bloated and had diarrhoea after eating some fish fried in flour (We made a mistake in ordering them but I didn't want to complain). My partner also reported that my mood swings (which I admit can be a little unpredictable) were much better. Once we started travelling I gave up and ate what I was given as we were staying with friends etc much of the time. Toward the end of our trip I started to feel extremely tired, to the point of having to stay in for "rest" days, and my guts were very unhappy. I chalked it up to irregular eating patterns, too many beers and late nights in general. During the trip I also had an extreme hangover after drinking wheat beer. And, while of course I accept that any overindulgence can make you ill, I really felt that that level of hangover was quite out of the ordinary. Finally, I developed a strange lump under my armpit during this period. Now back at home, I decided to go to the doc and check out the odd lump under my armpit. The doctor was pretty confident that it was nothing to worry about cancer-wise but she ordered a battery of blood tests just to be sure. The lump is fine (good news) but the results showed elevated GGT, high-ish ALT and normal AST liver enzymes plus signs of dehydration in red bloods / higher (but not concerning) levels of white bloods. I'm scheduled to go back for another blood test to double-check liver function and discuss results - if it is again high she will send me for a ultrasound. Does this history chime with anyone here? I know that the correct course in basic health terms is to stop drinking for some time (easily done) and stop smoking forever (easy to say...) but I cannot help but think that something else is going on here. I will discuss this with my doctor and make clear that my bowel issues have not been resolved and that the initial IBS diagnosis wasn't based on any thorough testing so to speak. In the meantime - does anyone have any advice for me in times of avenues to research or experience of similar symptoms? Gluten remains in my diet but in all other respects it could be regarded as very healthy, I think anyway... (pescatarian, plenty of fruit and veg, little to no sugar on a daily basis, not much dairy to speak of...) Thanks in advance and sorry for bending everyone's' ear about this... I guess it's just taken a long time for me to admit I might be sick and I need some help. Jen