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Anti transglutaminase antibodies cause ataxia in mice

Boscolo, Sabrina, Lorenzon, Andrea, Sblattero, Daniele, Florian, Florella, Stebel, Marco, Marzari, Roberto, Not, Tarcisio, Aeschlimann, Daniel, Ventura, Alessandro, Hadjivassiliou, Marlos and Tongiorgi, Enrico 2010. Anti transglutaminase antibodies cause ataxia in mice. PLoS ONE 5 (3) , e9698. 10.1371/journal.pone.0009698

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Publisher: Public Library of Science
ISSN: 1932-6203
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 03:02

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