Anti transglutaminase antibodies cause ataxia in mice

Sabrina Boscolo, Andrea Lorenzon, Daniele Sblattero, Fiorella Florian, Marco Stebel, Roberto Marzari, Tarcisio Not, Daniel Aeschlimann, Alessandro Ventura, Marios Hadjivassiliou, Enrico Tongiorgi

Research output: Contribution to journalArticle

Abstract

Background: Celiac disease (CD) is an autoimmune gastrointestinal disorder characterized by the presence of antitransglutaminase 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.

Original languageEnglish
Article numbere9698
JournalPLoS One
Volume5
Issue number3
DOIs
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Boscolo, S., Lorenzon, A., Sblattero, D., Florian, F., Stebel, M., Marzari, R., Not, T., Aeschlimann, D., Ventura, A., Hadjivassiliou, M., & Tongiorgi, E. (2010). Anti transglutaminase antibodies cause ataxia in mice. PLoS One, 5(3), [e9698]. https://doi.org/10.1371/journal.pone.0009698