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.