CD8(+)/perforin/granzyme B(+) effector cells infiltrating cerebellum and inferior olives in gluten ataxia.
Up to 8% of patients with gluten sensitivity (GS) develop neurological symptoms such as ataxia, dementia, seizures or peripheral neuropathy. The underlying immunological mechanisms still remain to be elucidated. We here report the case of a 68-year-old male patient suffering from progressive ataxia and dementia associated with chronic diarrhea and both elevated IgG and IgA antigliadin-antibodies. At autopsy, frequent argyrophilic glial and neuronal inclusions within the basal nucleus of Meynert were considered as the structural correlative for the cognitive decline. Significant neuronal loss in the cerebellar cortex and the inferior olives was accompanied by infiltrating CD8(+)/perforin(+)/granzyme B(+) cells as well as reactive astrogliosis and microglial activation. These CD8(+) cytotoxic T and NK cells are likely to act as effector cells responsible for neuronal cell death in patients with gluten sensitivity and neurological disease and might therefore at least partly be responsible for cerebellar symptoms in gluten ataxia. In conclusion, our results, showing an absence of B- or plasma cells but multiple CD8(+) as well as granzyme B and perforin expressing cells in ataxia-associated brain areas, suggest that there are also prominent cytotoxic effects in neuropathogenesis of GS.
Mittelbronn
Michel
M
Institute of Brain Research, University of Tübingen, Tübingen, Germany. michel.mittelbronn@kgu.de
Schittenhelm
Jens
J
Bakos
Gellert
G
de Vos
Rob A
RA
Wehrmann
Manfred
M
Meyermann
Richard
R
Bürk
Katrin
K
D000368:Aged; D001253:Astrocytes / Q000473:pathology / Q000648:ultrastructure; D001259:Ataxia / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016827:CD8 Antigens / Q000378:metabolism; D002446:Celiac Disease / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017809:Fatal Outcome; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D017628:Microglia / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D009847:Olivary Nucleus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D054353:Perforin / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
D016827:CD8 Antigens; D054353:Perforin; D053804:Granzymes