An investigation of the humoral immune response in patients with gluten ataxia.

It is now well established that gluten sensitivity comprises a spectrum of disorders, which affect different target organs. The small-intestine (coeliac disease), skin (dermatitis herpetiformis) and peripheral and central nervous systems are most frequently affected. These manifestations may occur alone or in combination with one another.Neurological complications affect approximately 6-10% of patients with gluten sensitivity with ataxia being the most frequent disorder seen in these patients. It has recently been established that previously undiagnosed gluten sensitivity may present solely with ataxia (gluten ataxia) and this disease entity may account for a large number of patients with sporadic idiopathic ataxia. Preliminary findings suggest an immune pathogenesis for gluten ataxia, in common with other manifestations of gluten sensitivity. The studies in this thesis are concerned with investigation of the humoral immune response in the pathogenesis of gluten ataxia.Assessment using enzyme-linked immunosorbent assay, immunohistochemistry and western blotting has shown the presence of elevated levels of circulating gluten sensitivity associated antibodies (anti-gliadin and anti-tissue transglutaminase antibodies) in patients with gluten ataxia. Studies have also shown the cross-reaction of anti-gliadin antibodies with epitopes on cerebellar Purkinje cells. In addition, patients with gluten ataxia possess circulating antibodies directed against cerebellar Purkinje cells, which are distinct from anti-gliadin antibodies although the target antigen remains unknown. Finally, studies have also shown that patients with gluten ataxia have elevated levels of circulating antibodies directed against glutamic acid decarboxylase.These studies suggest a role for the humoral immune response in gluten ataxia. However, preliminary evidence is also suggestive of a T-cell mediated response and the relative contributions of each in the pathogenesis of gluten ataxia remains to be elucidated.