{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:32:02Z","timestamp":1786609922545,"version":"build-2736575974"},"reference-count":28,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Gluten ataxia (GA) is the most common neurological manifestation of gluten sensitivity. GA is identified by serological evidence of gluten sensitivity when other defined causes for ataxia have been excluded. Whilst there are several serological markers for gluten sensitivity, antibodies against transglutaminase enzyme 6 (anti-TG6) are of particular interest as it is the autoantigen in GA. Our objective was to assess the value of a commercial anti-TG6 ELISA assay in routine clinical practice for the investigation and management of patients with progressive ataxia. Methods: Patients with progressive ataxia underwent standardized clinical and detailed investigative workup. Anti-TG6 was measured using a commercial ELISA assay. Patients with ataxia who were seropositive for any gluten sensitivity-related antibody were offered dietary advice for a gluten-free diet. All patients underwent baseline and follow-up MR spectroscopy scans of the cerebellum. Results: 155\/161 (96%) patients with GA diagnosed on the basis of circulating antigliadin antibodies (the original definition of gluten ataxia) were also positive for anti-TG6. In total, 329\/425 (77%) patients with idiopathic sporadic ataxia, all other causes of ataxia excluded, were positive for anti-TG6 alone. 115\/296 (39%) patients with ataxia due to genetic causes were positive for anti-TG6, as were 17\/59 (29%) patients with a clinically established cerebellar variant of multi-system atrophy. Amongst patients with other neurological conditions (non-ataxia), anti-TG6 was found in 13%, compared with 50% of patients with coeliac disease presenting to gastroenterologists. Overall, 146 patients with ataxia and anti-TG6 alone responded to a gluten-free diet, with a reduction\/elimination of TG6 antibodies and improved MR spectroscopy. Patients with an identified genetic ataxia and anti-TG6 did not show a significant response to a gluten-free diet. Conclusions: Anti-TG6 appears to be a more sensitive diagnostic marker for GA when compared to antigliadin antibodies. Patients with ataxia and isolated anti-TG6 benefit from a strict gluten-free diet.<\/jats:p>","DOI":"10.3390\/nu18162645","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:06:16Z","timestamp":1786608376000},"page":"2645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antibodies to Transglutaminase-6 Identify Ataxia Responsive to Gluten-Free Diet"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2542-8954","authenticated-orcid":false,"given":"Marios","family":"Hadjivassiliou","sequence":"first","affiliation":[{"name":"Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1442-8887","authenticated-orcid":false,"given":"Richard A.","family":"Gr\u00fcnewald","sequence":"additional","affiliation":[{"name":"Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0987-9440","authenticated-orcid":false,"given":"Iain D.","family":"Croall","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6447-7639","authenticated-orcid":false,"given":"Nigel","family":"Hoggard","sequence":"additional","affiliation":[{"name":"Department of Infection and Immunity, University of Sheffield, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme","family":"Wild","sequence":"additional","affiliation":[{"name":"Department of Immunology, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8567-3092","authenticated-orcid":false,"given":"Panagiotis","family":"Zis","sequence":"additional","affiliation":[{"name":"Medical School, University of Cyprus, Nicosia 2029, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Shanmugarajah","sequence":"additional","affiliation":[{"name":"Academic Department of Neurosciences, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Sheffield Teaching Hospitals NHS Trust, Sheffield S10 2JF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/S0140-6736(98)05342-2","article-title":"Clinical, radiological, neurophysiological and neuropathological characteristics of gluten ataxia","volume":"352","author":"Hadjivassiliou","year":"1998","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/nm0797-797","article-title":"Identification of tissue transglutaminase as the autoantigen of celiac disease","volume":"3","author":"Dieterich","year":"1997","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1084\/jem.20011299","article-title":"Epidermal transglutaminase (TGase3) is the autoantigen of dermatitis herpetiformis","volume":"195","author":"Merkl","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"59","DOI":"10.14309\/ajg.0000000000002075","article-title":"American College of Gastroenterology guidelines update: Diagnosis and management of celiac disease","volume":"118","author":"Hill","year":"2023","journal-title":"Am. J. Gastroenterol."},{"key":"ref_5","first-page":"209","article-title":"The serological diagnosis of coeliac disease\u2014A step forward","volume":"11","author":"Holmes","year":"2018","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1053\/j.gastro.2018.12.010","article-title":"AGA Clinical practice Update on the diagnosis and monitoring of celiac disease: Changing utility of serology and histologic measures","volume":"156","author":"Husby","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_7","first-page":"118","article-title":"The role of serology in the diagnosis of coeliac disease","volume":"16","author":"Volta","year":"2023","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s00415-025-13187-w","article-title":"Serological analysis of gluten-related antibodies in idiopathic neuropathies and cerebellar ataxia","volume":"272","author":"Rouvroye","year":"2025","journal-title":"J. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s00726-010-0554-y","article-title":"Gluten T cell epitome targeting by Tg3 and Tg6; implications for dermatitis herpetiformis and gluten ataxia","volume":"39","author":"Stamnaes","year":"2010","journal-title":"Amino Acids"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1038\/nrm1014","article-title":"Transglutaminases: Crosslinking enzymes with pleiotropic functions","volume":"4","author":"Lorand","year":"2003","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.1016\/j.cgh.2019.03.014","article-title":"Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to transglutaminase 6","volume":"17","author":"Hadjivassiliou","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/ana.78020","article-title":"Hoggard Persisting transglutaminase 6 antibodies in neurological gluten-related disorders","volume":"99","author":"Croall","year":"2025","journal-title":"Ann. Neurol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1136\/jnnp-2018-318215","article-title":"Serum antigliadin antibodies in cerebellar ataxias: A systematic review and meta-analysis","volume":"89","author":"Lin","year":"2018","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.cca.2010.09.042","article-title":"IgA-class auto-antibodies against neuronal transglutaminase, TG6 in celiac disease: No evidence for gluten dependency","volume":"412","author":"Lindfors","year":"2011","journal-title":"Clin. Chim. Acta."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1136\/jnnp.74.9.1221","article-title":"Dietary treatment of gluten ataxia","volume":"74","author":"Hadjivassiliou","year":"2003","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_16","first-page":"OD07","article-title":"Gluten sensitivity-A potentially reversible cause of progressive cerebellar ataxia and myoclonus","volume":"9","author":"Khwaja","year":"2015","journal-title":"J. Clin. Diag. Res."},{"key":"ref_17","first-page":"268","article-title":"Think of gluten ataxia: A rare but potentially reversible cause of progressive neurological disorder","volume":"34","author":"Mathur","year":"2019","journal-title":"Mov. Disord."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e262288","DOI":"10.1136\/bcr-2024-262288","article-title":"Paediatric gluten ataxia: A rare neurological presentation of gluten sensitivity in a toddler","volume":"18","author":"Rasool","year":"2025","journal-title":"BMJ Case Rep."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Alahiane, Z., Tahiri, F., Bourrahouat, A., El Qadiry, R., Nassih, H., and Sab, I.A. (2021). Gluten Ataxia: Cerebellar ataxia complicating celiac disease: A case report in pediatrics. Sch. J. Med. Case Rep.","DOI":"10.36347\/sjmcr.2021.v09i11.006"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"173","DOI":"10.12691\/ijcd-5-4-10","article-title":"Ataxia triggered by gluten","volume":"5","author":"Rahmoune","year":"2017","journal-title":"Int. J. Celiac Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/BF00314115","article-title":"Progressive cerebellar syndrome in adult coeliac disease","volume":"234","author":"Kristoferitsch","year":"1987","journal-title":"J. Neurol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/BF00314464","article-title":"Myoclonus and adult celiac disease","volume":"236","author":"Tison","year":"1989","journal-title":"J. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1136\/pgmj.67.793.1023","article-title":"Coeliac disease presenting with cerebellar degeneration","volume":"67","author":"Hermaszewski","year":"1991","journal-title":"Postgrad. Med. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1136\/pgmj.71.833.186","article-title":"Cerebellar ataxia in coeliac disease\u2014No evidence of a humoral aetiology","volume":"71","author":"Dick","year":"1995","journal-title":"Postgrad. Med. J."},{"key":"ref_25","first-page":"1","article-title":"Anti-gliadin and anti-tissue transglutaminase antibodies in the serum of patients with cerebellar ataxia","volume":"4","author":"Kumari","year":"2025","journal-title":"Int. Clinc. Med. Case Rep. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1093\/schbul\/sbs064","article-title":"Increased prevalence of transglutaminase 6 antibodies in sera from schizophrenia patients","volume":"39","author":"Cascella","year":"2012","journal-title":"Schizophr. Bull."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/s00415-017-8400-8","article-title":"No association between gluten sensitivity and amyotrophic lateral sclerosis","volume":"264","author":"Visser","year":"2017","journal-title":"J. Neurol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1001\/jamaneurol.2015.48","article-title":"Transglutaminase 6 antibodies in the serum of patients with amyotrophic lateral sclerosis","volume":"72","author":"Gadoth","year":"2015","journal-title":"JAMA Neurol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/16\/2645\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T08:25:55Z","timestamp":1786609555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/16\/2645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":28,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["nu18162645"],"URL":"https:\/\/doi.org\/10.3390\/nu18162645","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]}}}