CSF markers of TG6 autoimmunity in gluten ataxia

Gluten ataxia (GA) is the primary neurological manifestation of gluten sensitivity, characterised by loss of Purkinje cells throughout the cerebellar cortex and rooted in autoimmunity to transglutaminase 6 (TG6). Previous studies have shown the contribution of serum anti-TG6 antibodies to disease progression; however, it remains unclear where these antibodies are produced and how they gain access into the brain parenchyma. This study aims to provide an immunological assessment of the CSF in patients with GA to better define the humoral response contributing to disease pathophysiology. In this observational study we assessed the presence of plasma cells in the CSF of 20 patients with GA and 6 controls. CSF from 16 of the GA patients and from all 6 controls was investigated for the presence of anti-TG6 IgA antibodies. Immunohistochemistry for CD138 was performed to assess the presence of plasma cells in the cerebellum and spinal cord of 4 cases with GA, 4 ataxia controls and 4 neurologically healthy controls. A significant increase in anti-TG6 IgA antibodies was detected in the CSF of patients with GA compared to controls, with no correlation between CSF and serum levels of anti-TG6 IgA antibodies for either experimental group. CD138+ cells were present in the CSF of 2 patients with GA and in the cerebellum and spinal cord of 3 post-mortem cases of GA. In a subpopulation of patients with GA intrathecal presence of plasma cells and TG6 antibodies is a feature of the disease, likely associated with prolonged disease duration and continuous exposure to gluten.