%0 Journal Article %J PLoS One %D 2010 %T Anti transglutaminase antibodies cause ataxia in mice. %A Boscolo, Sabrina %A Lorenzon, Andrea %A Sblattero, Daniele %A Florian, Fiorella %A Stebel, Marco %A Marzari, Roberto %A Not, Tarcisio %A Aeschlimann, Daniel %A Ventura, Alessandro %A Hadjivassiliou, Marios %A Tongiorgi, Enrico %K Adult %K Animals %K Antibodies %K Ataxia %K Autoimmune Diseases %K Brain %K Celiac Disease %K Female %K Gliadin %K Humans %K Isoenzymes %K Male %K Mice %K Mice, Inbred C57BL %K Middle Aged %K Motor Skills %K Rats %K Rats, Sprague-Dawley %K Transglutaminases %X

BACKGROUND: Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of anti-transglutaminase 2 (TG2) and anti-gliadin antibodies. Amongst the neurological dysfunctions associated with CD, ataxia represents the most common one.

METHODS: We analyzed by immunohistochemistry, the anti-neural reactivity of the serum from 20 CD patients. To determine the role of anti-TG2 antibodies in ataxia, two anti-TG2 single chain variable fragments (scFv), isolated from a phage-display IgA antibody library, were characterized by immunohistochemistry and ELISA, and injected in mice to study their effects on motor coordination. We found that 75% of the CD patient population without evidence of neurological involvement, has circulating anti-neural IgA and/or IgG antibodies. Two anti-TG2 scFvs, cloned from one CD patient, stained blood vessels but only one reacted with neurons. This anti-TG2 antibody showed cross reactivity with the transglutaminase isozymes TG3 and TG6. Intraventricular injection of the anti-TG2 or the anti-TG2/3/6 cross-reactive scFv provoked transient, equally intensive ataxia in mice.

CONCLUSION: The serum from CD patients contains anti-TG2, TG3 and TG6 antibodies that may potentially cause ataxia.

%B PLoS One %V 5 %P e9698 %8 2010 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/20300628?dopt=Abstract %R 10.1371/journal.pone.0009698