Improving the diagnosis and management of gluten ataxia

Professor Marios Hadjivassiliou is an NHS Consultant Neurologist whose primary research focus is on the neurological manifestations of gluten related diseases. Part of his research resulted in defining gluten ataxia and eventually led to developing a diagnostic test for the condition. He is also the Director of the Sheffield Ataxia Centre, where he cares for over 3000 patients with forms of ataxia.

Ataxia is a term for a group of conditions that affect balance, speech, and coordination. Over the last 25 years, research at the Sheffield Teaching Hospitals NHS Trust has identified a cohort of patients whose unexplained ataxia is due to gluten sensitivity (gluten ataxia).

Professor Hadjivassiliou explains “Gluten ataxia is a serious autoimmune condition where gluten ingestion causes damage to the cerebellum; the part of the brain which coordinates balance and speech. It can occur with coeliac disease or independently, and the only treatment is a strict gluten free diet for life. Early diagnosis is crucial to prevent permanent, long term damage and functional issues with speech, balance and coordination.”

Ongoing research at the Sheffield Institute of Gluten Related Disorders has led to the development of a new diagnostic blood test using a previously defined marker of gluten ataxia, transglutaminase 6 (TG6) antibodies. This is used over and above antigliadin antibodies that are also of diagnostic use in gluten ataxia. This blood test has been made readily available under the NHS in Sheffield, but is not yet available at other laboratories in the UK. Routine blood tests for coeliac disease are typically offered, but these lack sensitivity for gluten ataxia, meaning the majority of cases may go unrecognised. This project aimed to provide evidence for the wider use of the diagnostic test by demonstrating its value in identifying patients with gluten ataxia.

Jointly funded by Coeliac UK, Ataxia UK and Sheffield Hospitals Charity, the project was a collaborative study supported by consultant neurologists from other ataxia centres across the UK (London, Oxford and Manchester). Patients with unexplained forms of idiopathic sporadic ataxia (ISA), were recruited to investigate whether a proportion of these cases could be gluten ataxia. Previous research has shown that around 40% of ataxias where no other cause is found could actually be gluten ataxia.

A total of 103 patients from across the UK were referred to Professor Hajivassiliou’s team at the Sheffield Ataxia Centre for testing as part of this project. These were patients without a diagnosis of the cause of their ataxia.

Preliminary results have shown that out of 103 patients, 57 were confirmed to have no cause of their ataxia after full investigation. Among these cases, a positive TG6 and/or antigliadin antibody was found in 79% of patients. After diagnosis, patients were offered brain imaging, followed by referral to dietetic services for advice regarding the gluten free diet. It has already been shown that patients with gluten ataxia improve on a gluten free diet. By demonstrating the value of this diagnostic approach there will be a push for wider adoption of these tests, enabling more people to receive an accurate diagnosis and access treatment through a strict gluten free diet.

The study also provided insights into how gluten ataxia affects the brain. The team examined brain tissue and compared it to healthy and ataxia control tissue. There were distinct differences between these groups with gluten ataxia tissue showing evidence of inflammation and altered cellular processes responsible for breaking down proteins and producing energy. By improving our understanding of the biological changes that occur in gluten ataxia, this research could help identify new targets for treatment and support the development of more effective therapies in the future.

Professor Hadjivassiliou and his team are now focused on publishing these findings and working towards making the diagnostic test more widely available across immunology laboratories in the UK. A collaborative approach involving Coeliac UK and Ataxia UK has been proposed to support implementation and raise awareness of the value of diagnosing gluten ataxia. The research team is also continuing to investigate the role of TG6 to further understand the mechanisms of this disease.