Coeliac disease patients do not produce antibodies to a common cerebellar epitope.
BACKGROUND
Most adult-onset sporadic ataxias are unexplained, and the claim that many of these may be a result of gluten sensitivity has led to uncertainty as to whether to test for anti-gliadin antibodies (αGAb) and, if present, whether to recommend a gluten-free diet or continue searching for other causes of ataxia. This uncertainty arises in part from the frequency of αGAb in the population (about 1 in 10), but recent work delineating transglutaminase 6 as the target antigen in gluten ataxia has clarified the situation somewhat. Our aim was to determine whether there is molecular mimicry between cerebellar Purkinje cell antigens and gluten in subjects selected for recent diagnosis of CD rather than for ataxia.


RESULTS
High titre αGAb sera from 11 newly-diagnosed CD patients and normal sera from 10 healthy controls were used to detect cross-reacting antibodies to cerebellar and cerebral cortex antigens in mouse, monkey and human tissue. None of the CD patients displayed ataxia. Mouse and human cerebellar and cerebral cortex extracts were analysed by Western blot probed with CD and control sera. Immunofluorescence microscopy was used on mouse and monkey cerebellar sections immunostained with CD and control sera to detect cross-reacting IgG antibodies. Western blot analysis of cerebellar and cerebral cortex extracts probed with CD sera did not demonstrate any specific immunoreactivity unique to the cerebellum. An identical twin pair with CD produced different patterns of reactivity. Immunofluorescence staining of mouse and monkey cerebellar sections showed most control and CD sera reacted non-specifically, with the exception of two CD and one control sera, each having a unique staining pattern.


CONCLUSIONS
CD patient sera with high titre αGAb do not detect a common Purkinje cell or cerebellar-specific epitope. The pattern of reactivity is not solely dependent on genetic background.
Department of Medicine (Neuroscience), Monash University, (Alfred Hospital Campus), Commercial Road, Melbourne, VIC 3004 Australia.
Volga
V
Tarlac
Department of Medicine (Neuroscience), Monash University, (Alfred Hospital Campus), Commercial Road, Melbourne, VIC 3004 Australia.
Louise
L
Kelly
ImmusanT, Inc. One Kendall Square, Suite B2004, Cambridge, MA 02139 USA.
Robert P
RP
Anderson
The Alfred Hospital, National Trauma Research Institute, Melbourne, VIC 3004 Australia.
Nicole
N
Bye
Department of Medicine (Neuroscience), Monash University, (Alfred Hospital Campus), Commercial Road, Melbourne, VIC 3004 Australia.
Elsdon
E
Storey
Anti-gliadin; Ataxia; Cerebellum; Coeliac disease; Gluten ataxia; Purkinje cell