title: HLA-DR3-DQ2 mice do not develop ataxia in the presence of high titre anti-gliadin antibodies.
abstract: Recently, it has been suggested that anti-gliadin antibodies (αGAb) may produce "gluten ataxia", even in the absence of celiac disease enteropathy. αGAb are reportedly present in 12-50 % of patients with sporadic ataxia, but also in 12 % of the general population, such that the importance of αGAb as a cause of sporadic ataxia is not conclusively settled. We aimed to determine whether mice transgenic for HLA-DR3-DQ2 and immunised with gliadin to achieve high titres of αGAb would develop ataxia and/or cerebellar damage. From 6 weeks of age, HLA-DR3-DQ2 transgenic mice were immunised fortnightly with gliadin (n = 10) or a saline control (n = 6) in adjuvant. Serum titres were measured by αGAb enzyme-linked immunosorbent assay. At 24 weeks of age, mice were tested for locomotor function using the accelerating rotarod, ledged beam, ink-paw gait, and several neurological severity score subtests. Brains were then collected and processed for immunohistochemistry. Sections were analysed for lymphocytic infiltration, changes in morphology and Purkinje cell (PC) dendritic volume and the number of PCs counted via unbiased stereology. Gliadin-immunised mice developed high αGAb titres while controls did not. There was no statistically significant difference between the gliadin and sham-immunised HLA-DR3-DQ2 mice on any of the tests of motor coordination, in lymphocytic infiltration, PC number or in dendritic volume. High levels of αGAb are not sufficient to produce ataxia or cerebellar damage in HLA-DR3-DQ2 transgenic mice.
authors.affiliation: Department of Medicine and Van Cleef Roet Centre for Nervous Disease, Monash University (Alfred Hospital Campus), Commercial Road, Melbourne, VIC 3004, Australia.
authors.forename: Volga
authors.initials: V
authors.lastname: Tarlac
authors.forename: Louise
authors.initials: L
authors.lastname: Kelly
authors.forename: Nupur
authors.initials: N
authors.lastname: Nag
authors.forename: Judy
authors.initials: J
authors.lastname: Allen-Graham
authors.forename: Robert P
authors.initials: RP
authors.lastname: Anderson
authors.forename: Elsdon
authors.initials: E
authors.lastname: Storey
mesh_terms: D000367:Age Factors; D000818:Animals; D000906:Antibodies / Q000097:blood*; D001259:Ataxia / Q000097:blood / Q000235:genetics / Q000276:immunology; D002452:Cell Count; D002531:Cerebellum / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D008124:Locomotion / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011689:Purkinje Cells; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics / Q000276:immunology
chemical_list: D000906:Antibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D015803:HLA-DR3 Antigen; D005903:Gliadin