Gluten Ataxia – Passive Transfer in a Mouse Model (1)
Celiac disease [CD] is accompanied by the production of anti- gliadin (AGA) and anti-tissue transglutaminase (TGase2) antibodies. Gluten ataxia (GA) was described as patients with idiopathic ataxia presenting with circulating AGA antibodies.
Two rodent models spontaneously develop type 1 diabetes, the nonobese diabetes (NOD) mice and BioBreeding (BB) rats. As diabetes is highly associated with CD, these animal models are interesting for the study of autoimmune pathologies correlated with gluten sensitivity. They do not, however, show any mucosal intestinal alterations or anti-AGA or anti-TGase2 antibodies. NOD mice do produce anti-GAD and anti-insulin antibodies.
Two sera samples from patients with CD without neurological complications but positive for anti-neural antibodies showed a mild effect that reached statistical significance for the CD2 serum at 3 h after injection. GA patient was positive for AGA and anti-neural IgG antibodies. Staining with the serum CD1 was restricted to the nuclei, serum CD2 showed the same nuclear staining with a mild cytoplasmic staining, whereas the GA patient’s serum showed a diffused cytoplasmic but no nuclear staining.
The two purified antibodies were injected separately, into mice lateral brain ventricle, and motor performance of the injected animals was measured on the rotarod at 1, 3, 6, and 24 h after injection. Mice tested on the elevated plus maze (3 h after injection) showed a mild increase in anxiety compared to mice treated with bac1, but the difference was not statistically significant.
The light–dark box test, run 4 h after antibodies injection, did not show significant differences between the two anti-TGase2 antibodies and the control bac1, besides a small anxiogenic effect of class1. In the open field test, carried out 5 h after injection, the distance covered and the thigmotaxis parameter were not different among mice treated with the three antibodies
In GA patients there are deposits of anti-TGase2 antibodies on brain vessels,28 supporting the hypothesis that both class1 and class2 anti-TGase2 antibodies affect the functioning of the blood–brain barrier. It would be interesting to inject AGA, anti-TGase2, and anti-neural antibodies in animal models, such as NOD mice, to prove their pathogenicity in a situation more analogous to human gluten sensitivity.