New paper published on TG6 antibodies and patient outcomes in Gluten-related neurological disorders

Gluten-related disorders, also known as gluten sensitivity disorders, happen when a person’s immune system reacts to gluten, and immune cells called autoantibodies, mistakenly attack the body’s tissues. This is called an autoimmune response. There are numerous autoantibodies that can be produced in response to gluten. Some gluten-related conditions affect the nervous system (brain and nerves), such as Gluten ataxia. These are called neurological gluten-related disorders. In Gluten ataxia, it is thought that the immune system produces antibodies associated with nervous system cells, and patients suffer from ataxic symptoms. Coeliac Disease (CD) is a more commonly known gluten-related disorder which affects the gut. People can have both CD and neurological gluten-related disorders, but gluten-related neurological disorders can also exist on their own.  

Transglutaminase 6 (TG6) is an enzyme found in high quantities in the nervous system, including in some neurons in the brain. Enzymes help with processes in the body. If the body produces autoantibodies to target TG6 when it is exposed to gluten, this affects the TG6 enzyme function. Prof Hadjivassiliou and his colleagues at the Sheffield Teaching Hospitals NHS Trust have identified TG6 autoantibodies as a biological marker to diagnose and monitor the progression of Gluten ataxia. When TG6 autoantibodies are present in people with CD, it has been associated with negative effects on the brain. TG6 autoantibodies can be detected via a blood test. Currently, the best way to diagnose and monitor gluten-related neurological conditions is not clear. Diagnosis involves ensuring that there is no other cause for symptoms and checking for gluten-related autoantibodies in the blood. Treatment is with a gluten-free diet.  

This research, conducted at the Sheffield Ataxia Centre, investigated whether testing people for TG6 autoantibodies in the blood could help with diagnosing and monitoring gluten-related neurological conditions. The researchers did this by evaluating if there was a link between having TG6 antibodies in the blood and patient outcomes and brain scan findings in people with gluten-related neurological disorders, with and without CD. 

Results found that having tested positive for TG6 autoantibodies (by testing IgA TG6 levels in the blood), at any point during a patient’s time in the gluten ataxia clinic, was linked to several negative outcomes – such as the speed at which the brain shrank over time, patients’ reported symptom severity, mood and physical functioning. For people who had a previous positive TG6 autoantibody test, greater adherence to a gluten-free diet predicted a negative TG6 autoantibody test result on recent testing.  

The study therefore recommends IgA TG6 blood testing to help with diagnosis and monitoring for people with gluten-related neurological conditions, with or without CD; and that IgA TG6 monitoring should be undertaken when people are treated with a gluten-free diet, aiming for no detectable TG6 autoantibodies on blood testing. Further research should investigate whether TG6 testing should also be undertaken in all people with CD to help identify those more at risk of neurological complications.   

Ataxia UK has co-funded a project on improving the diagnosis and management of Gluten ataxia, in partnership with Coeliac UK and the Sheffield Trust, which you can read about here. If you or someone you know has had tests to rule out other types of ataxias and do not have a diagnosis of the cause of ataxia, you could be referred to the Sheffield Ataxia Centre to be tested for gluten ataxia. If you are diagnosed with gluten ataxia, you can take part in the study, where you will follow a strict gluten-free diet. You will then be followed up after one year to assess the impact of the gluten-free diet.  

Read more here about how to take part.