Cerebellar degeneration in gluten ataxia is linked to microglial activation

Abstract

Gluten sensitivity has long been recognised exclusively for its gastrointestinal involvement, however more recent research provides evidence for the existence of neurological manifestations that can appear in combination with, or independent of the small bowel manifestations. Amongst all neurological manifestations of gluten sensitivity, Gluten ataxia is the most commonly occurring one, accounting for up to 40% of cases of idiopathic sporadic ataxia. However, despite its prevalence, its neuropathological basis is still poorly defined. Here we provide a neuropathological characterisation of gluten ataxia and compare the presence of neuroinflammatory markers GFAP, Iba-1, MHC-II and CD68 in the central nervous system of 4 gluten ataxia cases to 5 ataxia controls and 7 neurologically healthy controls. Our results demonstrate that severe cerebellar atrophy, CD20+ and CD8+ lymphocytic infiltration in the cerebellar grey and white matter and a significant upregulation of microglial immune activation in the cerebellar granular layer, molecular layer, and cerebellar white matter are features of Gluten ataxia, providing evidence for the involvement of both cellular and humoral immune-mediated processes in gluten ataxia pathogenesis.