Antibodies to Transglutaminase-6 Identify Ataxia Responsive to Gluten-Free Diet

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.