Gluten sensitivity and brain disease: neuronal transglutaminase

The authors of this paper published in Annals of Neurology make an important statement:

"Gluten sensitivity typically presents as celiac disease, a chronic, autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity."

Antibodies directed toward transglutaminase in the gut are a well-known diagnostic feature of celiac disease. These investigators have identified another member of the transglutaminase family:

"...a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction." They found that "Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement."

(Ataxia is loss of the ability to coordinate muscle movement, especially as it appears with difficulty walking.) Their conclusion:

"Antibodies against transglutaminase 6 can serve as a marker...to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease."

If you are gluten sensitive, you can have neurological disease without celiac involvement.