Anti-tranglutaminase-6 antibody test - Gluten Sensitivity Test

Hi there, I'm just seeing this, I registered just to reply to you. Did you ever find a US lab that does the TG6 test? I was diagnosed with Sporadic Idiopathic Cerebellar Ataxia in 2017 by neurologists at the University of Michigan. They ruled out genetic and can't identify the cause of my ataxia, so they just call it Origin Unknown. Honestly, they don't seem to be trying too hard to find the root of it, and these geniuses don't believe that Gluten Ataxia even exists. I'm pretty sure that I have GA, and like you I have studied Prof Hadjivassiliou's research, which speaks to me. I'm going to go gluten free soon, but I want to take the TG6 test first to find out what my levels are and then retest after being gluten free for a year. But I cannot find a lab here. I'm currently communicating via email with the Ataxia Centres UK to see if they can work with an American. They're checking but no word yet. Did you find anywhere here?

Thank you for your posts about the TG6 test. I, too, saw the webinar with the doctor from Sheffield University and was intrigued. I have had on and off "flares"of leg paralysis, debilitating hip joint pain, and muscle spasms for the past twelve years (no GI issues). For the past five months I have not been able to walk other than shuffle around my house. I have seen three neurologists among many other specialists over the years. I seem to be ruled out for MS and Lupus, Lyme etc but they finally found that my tTG Transglutaminase is >100. I will have an endoscopy soon and was hoping to have this TG6 test done.... But my GI has never seen a patient with my symptoms before and has never heard of gluten ataxia. I wish I could see a neurologist who studies gluten ataxia, but I'm quickly finding that not many have ever heard of this! Hoping that somehow many voices speaking up can help to bring about awareness of the "realness" of this condition. Thank you for writing.... It helps to know that others are out there!

Hi,

I am very similar to you. Diagnosed in 2023 and suspecting I have a sensitivity to gluten. U.S neurologists don’t have any knowledge of gluten ataxia research. I am gluten free now since November. I am looking to go anywhere for a tg6 test. I am not celiac, have tested negative for other gluten markers. But have a strong feeling due to other symptoms. Did you have any luck with finding a way to get the tg6 test. I am a Canadian in North Carolina.

Hey there,
I completely forgot about posting here until you replied. I too am gluten free since Nov. No, I never did find a lab in the US that does the TG6 test, I don't think there are any. I connected with an ataxia clinic in the UK who tried to find a lab here that does it but they could not, and they can't work with an American or anyone outside the UK national health system. It turns out that the test is even quite specialized in the UK with only two labs that do it, both at ataxia clinics. I only wanted to take the test to find out my TG6 levels and then compare after a year GF, but it (testing) wasn't mandatory for me to change my diet. How are you doing with it? It seems everyone freaks out about how hard going gluten free is, but after a few months I think it's pretty easy. I stay away from foods advertised as Gluten Free as they tend to have other ingredients that spike blood sugar levels. I just fill my diet with foods that are naturally gluten free. It took a little getting used to but wasn't crazy hard or anything. I live in Detroit MI on the Canadian border, have lots of good friends across the river and go there often:)

I, too, reached out to Sheffield UK to see if they could recommend a testing center or a neurology group that would help with the diagnosis of gluten ataxia. They were sorry to tell me that the only advice they could give was to try and talk with my doctors about this test. I am finally diagnosed with Celiac, as of yesterday, and am finally going gluten free today. My new GI has never seen anyone with paralysis or ataxia related to CD, but she does not discount the possibility... she and my young daughter's pediatric GI both say that "gluten can cause anything". My daughter has also had issues with possible ataxia for the past three years. Of course we will not really ever know for sure, but if symptoms let up than we have a good hunch as to what has caused them. My GIrecommended a book "Celiac Disease: Hidden Epidemic by Peter H.R. Green M.D. and Rory Jones M.S. They are both from the Celiac Disease Center in Columbia University. This book is excellent and actually talks about gluten ataxia and paralysis (and many other potential symptoms!) It also talks about the fact that many neurological tests do not detect the paralysis or ataxia that gluten causes. I have appointments with my neurologist and plan to bring this book with me. There needs to be more awareness in the medical community about the realm of possible gluten intolerance/Celiac symptoms. My daughter and I have both been to at least twenty doctors, and very good doctors within their specialties, but only one doctor ever tested me for gluten... A hospitalist I only saw once. Very thankful. Are your symptoms improving since going gluten free? I am hoping my legs will improve... I've been limited to a shuffle for the past six months. Hoping going gluten free is helping you all.

I began the journey of this past year with notable cerebellar atrophy on an mri. It was present on an mri from 25 years ago, but had progressed significantly. Shortly after I began having difficulty walking and moving. And always had a complete weak and strange feelings in my legs. It was a constant weakness. Over the summer I was diagnosed with a functional movement disorder. And started trying to recover from that episode. In the fall my foot and hand numbness that I have always experienced got much worse. In November (just days after going gluten free) I was diagnosed with sensory neuropathy in hands and feet. Shortly after that those pains got much worse. By December my skin was always burning and painful. Now I have settled into being gluten free for 10 weeks. My neuropathy pains are very minimal and Infrequent. Starting before gluten free I started to see an improvement with my walking. So time was helping that but now I feel very good. I go several hours with normal feeling legs. I m not hurting as much at the end of the day and back to more of my normal routine. Of note, I had a rash and itch for 25 years that didn’t ever go away. It is now gone. So I’m certain gluten played a role. I m happy I had an emg when I did, because that is measurable if at the next test I have reversed the neuropathy damage. As for the brain , I may have a genetic sca which cannot be proven right now through genetics. Or at my next mri, we will find the thinning in my cerebellum to have stopped. Which I feel is a strong indicator that we found a source. Neurologists here don’t recognize the gluten piece. They say to sit tight until can diagnose my sca. However if I feel like cutting out gluten is easy enough, that I would hate to find out in several years when testing is available that this was my root cause and it could have been prevented.

I’ve done a lot of very recent research on this. This is long, but I’m trying to think through all that I’ve learned about this question:

I have a clinical diagnosis of Cerebellar Ataxia, with recent MRI evidence of atrophy. We’re starting genetic testing, but I have no known family history of ataxia.

Last year, I also started having significant GI issues. I had a lot of testing done and finally got in to see a gastroenterologist at the University of Virginia Medical Center a month ago. He ran a million tests. I was unaware that one of these was gluten antibody testing. I would have told him not to bother—I’d been gluten-free for 5+ years at that point and had multiple rounds of gluten antibody testing ordered by well-meaning but ill-informed doctors trying to find the source for my ataxia and other symptoms.

I originally went GF in 2016, when I was postpartum and developed a terrible rash that resembled dermatitis herpetiformis (the dermatological form of Celiac Disease). A senior dermatologist biopsied and tested the rash multiple times but was never able to diagnose it as dermatitis herpetiformis. I was not aware at the time that the biopsies were not properly handled (She biopsied lesions. DH has to be biopsied by looking at skin adjacent to lesions.) She ran gluten antibody bloodwork that came back as elevated but didn’t listen to me when I told her that I had gone GF as soon as the possibility of celiac disease was raised. She dismissed these results. Months later, a resident conducting a file review contacted me and asked me to confirm that I’d been GF at the time of testing. I confirmed, and he ordered a small bowel biopsy. That, too, was actually mishandled. The doctor found evidence of flattening of the villi, but the biopsies were negative. They should have retested, done additional bloodwork, or looked deeper in the small intestine. Instead, they told me I was free of celiac disease.

My overall health worsened in the following two years. I saw a functional medicine doctor, who took me off of gluten (but didn’t run testing). I’ve been GF ever since, but I share a household with gluten-consuming family and am not extremely strict about cross-contamination. After all, I’d been told by top doctors I didn’t have celiac disease!

Fast forward to last fall: I was getting a GI endoscopy and explained this history to the doctor. He told me (absolutely incorrectly) that if I ate gluten for a few days before the biopsy, he’d find damage when he did the procedure. He again biopsied and found no evidence of celiac disease—after five years on a GF diet.

So, by the time I saw the gastroenterologist at UVA, I knew for sure I didn’t have celiac disease. I would have told him not to bother running antibody bloodwork. He did, and the test was positive!

He looked at my whole medical history (raised antibody levels even when maintaining a GF diet, unexplained neuropathy, current major GI issues, skin rash that was never diagnosed but sure looked like dermatitis herpetiformis, visual evidence of villous atrophy in small bowel biopsy, worsening migraine, ataxia without family history) and concluded that I very well may have Celiac Disease. He explained that it can actually be very challenging to diagnose CD in some patients.

He would like for me to get the tTG6 testing done in Sheffield UK, but there’s no way to do so through the NHS. We’re looking to see if anyone is doing study trials in the US of the testing. My primary neurologist is also with the University of Virginia, and he is open to this line of inquiry but knows of no one conducting research in the area. I’m also seeing the Johns Hopkins Ataxia Center and have asked the director for her assistance. I’m also going to call the National Ataxia Foundation.

In the meantime, my gastroenterologist is planning to do genetic testing for celiac disease and to look for antibodies to Purkinje cells, which apparently show up in patients with Gluten Ataxia.

I’ll continue in another comment to make sure I can post this one
…

There are some things to think through, even if I were magically able to find the testing. I’ve been gluten free for 5+ years, so there’s risk in consuming sufficient gluten for serum antibody testing to be positive. My gastroenterologist has told me I’d need a much longer “gluten challenge” for serum antibody testing than for a small bowel biopsy, because damage to tissue shows up well before levels in the blood are high enough to show on tests. My neurologists have said only that they may be able to use IVIG therapy to reverse any new damage that occurs as a result, but there’s no guarantee that my insurer would pay for such experimental therapy nor that it would work. There’s very little clinical research on the use of immune therapies in ataxia believed to be caused by gluten. I don’t want to end up in a wheelchair just to prove a point. And Sheffield’s own research shows that some who test positive do not improve on a GF diet.

And I guess there is some doubt outside the UK about the validity of the tTG6 testing used in Sheffield. By current scientific standards, the testing has not been validated through clinical study. No offense or discredit is meant. I’m not a doctor or scientist, but I try to read all of the research (dictionary in hand) so that I can actively participate in my own medical care. It doesn’t sound like there’s anyone in the US medical community with a high degree of confidence in the testing. None of the celiac disease or ataxia experts in the US are pursuing this line of research. There have not been clinical multi-site trials of the test at other centers or in other countries (with large, randomized patient pools and following all of the principles of valid medical study). I’ve seen journal articles where Professor Hadjivassiliou has used the test in other countries for celiac disease related conditions and some small-scale testing in schizophrenia ten years ago in the US (and we’ll follow up with the primary researcher, who’s in a neighboring state), but no evidence of widespread adoption of tTG6 testing for gluten ataxia or attempts to validate the results independently at other sites. Indeed, it’s not possible to do this type of study of the Sheffield tTG6 test, no matter how exciting the research may be. In order to for a study to validate a new diagnostic test there must be independent, blind comparison with a reference “gold standard” of diagnosis. There is no reference standard for diagnosis for gluten ataxia because there’s no other way to test for it.

Unfortunately, there are some ataxia experts who question whether Sheffield’s results are correct. The center clearly has a significant patient pool with clinical diagnoses of Cerebellar Ataxia. They find elevated tTG6 in these patients. However, there remains some chance that these patients could have undiagnosed inherited ataxias or even ataxias for which tests do not yet exist. At the best ataxia centers in the US, roughly 40% of adult onset ataxia patients don’t have a clear diagnosis. (I see the head of the Johns Hopkins Ataxia Center, and this is according to her.) In addition, tTG6 could be elevated in the larger pool of ataxia patients or even just in the pool of patients with autoimmune ataxia. I believe some of the US experts point to the fact that anti-Purkinje cell antibodies also appear in gluten ataxia, meaning that these antibodies and not tTG6 could be at the root of this ataxia. Correlation does not equal causation. Healthy debate among medical experts is a good thing. I wish there were more research!

I also wish there were a way to get the test from a reputable medical institution in the US. As of now, there doesn’t appear to be. The Mayo Clinic apparently offered a tTG6 test as part of its lab catalog but has removed it, reportedly because ataxia experts have questioned testing validity. There’s one private self-pay lab, not used by large hospitals or covered by any insurance, that offers tTG6 testing in the US. The lab (Cyrex) does not appear to have any physician or scientist in a leadership or advisory role who is an expert in celiac disease, ataxia, or even dietary immunology. I could certainly pay them $400+ to test tTG6, but what this would prove? How does this lab even set their reference level for tTG6 if there’s no common testing for it? Maybe they use Sheffield’s values? Cyrex appears to serve mostly functional medicine doctors who want to order multiple food immunity testing. This does not give me any confidence in Cyrex’s testing, because multiple food immunity panels are not considered by the medical community to be a scientifically valid (research backed) method of determining food allergy or sensitivity. I’ve seen two excellent functional medicine physicians, both of whom have said such tests are bogus. Indeed, recent position papers from European and American allergy and immunology societies have discredited all multiple food IgG panels and stated that they are not appropriate for making a diagnosis of food allergy or sensitivity.

Even if I were to take the Cyrex test, it sounds like there may be some question about interpreting the meaning of any elevated tTG6 level in my case. The guidance from the Sheffield lab to other NHS centers notes that, “Care should be taken when interpreting results as TG6 antibodies may also be present in other conditions and in healthy patients (5%).” So, in theory, I could have another condition that elevated tTG6. There’s a 2020 article from Professor Hadjivassiliou noting that 39% of patients with dermatitis herpetiformis (DH) have elevated tTG6. Furthermore, in a recent journal article, Dr. Hadjivassiliou and other authors advise that “it is important to appreciate the correct utility [of blood antibody markers] in the context of diagnosing [Gluten Ataxia]. Some markers are specific to the presence of enteropathy, while others are sensitive to the whole spectrum of gluten-related disorders. [Gluten Ataxia] responds well to a strict gluten-free diet with the best outcomes observed in patients where the diagnosis and treatment have been made early, before the loss of cerebellar reserve and permanent ataxia.” It appears that I had intestinal enteropathy that was improperly diagnosed. I subsequently went gluten-free and have remained so. My most recent MRI shows cerebellar atrophy, so we’re not really talking about early diagnosis before permanent ataxia. If I were to have testing, I’d want experts like those in Sheffield to interpret each marker in the context of other markers and my symptoms.

I’d love to prove that I have gluten ataxia, because I don’t want to do expensive and unnecessary genetic testing or have the fear of ataxia hanging over my son and his eventual children. Also, a positive diagnosis would require my health insurer to pay for further testing and gluten-free medications. It also might help my family and friends understand how strict I need to be in maintaining no gluten exposure (I do not live in a GF home.). However, my neurologist has pragmatically pointed out that the knowledge wouldn’t change my ataxia treatment.

There’s a lab in Heidelberg, Germany that says that it will do the test. They invite inquiries in English. I’ve emailed, but there’s no answer thus far.

For those interested in this question, there was an article in the NY Times, dated 10/11/2014, by Moises Velasquez-Manoff, titled “Can Celiac Disease Affect the Brain?” The article describes some of the controversy in the US over the tTG6 testing, including a study by Mayo Clinic neuroimmunologist Andrew McKeon that found other (non-gluten) causes for the neurological findings in celiac patients. It’s a really good layperson’s guide to this issue.

Thank you "Moxieness" and "Mesty"for sharing your experiences and insight! I cannot tell you enough how much I appreciate it and I am so sorry for the things you've had to endure. I will try keep these things in mind as my daughter and I de-gluten ourselves. Hoping that we will see some improvement in the coming weeks/months... But surely will keep all you've shared in mind and share with my doctors as best I can. Right now my doctor is wondering if I should head to Boston for answers... But I'm not sure, and neither is she who to even try to see. I seem to be enzyme deficient (Aldolase and LDH)... Though one neurologist doesn't seem concerned because sometimes it can be normal. Even with full blown Celiac but I've never had a single inflammatory marker elevated and this LDH is actually deficient (this is often elevated with Celiac). Anyway... Hoping that whatever this is begins to clear up now that I've gone gluten free, so I can get my legs back. Anyway, thank you both for sharing your experiences and insight! 🙂