Anti transglutaminase antibodies cause ataxia in mice

Boscolo, Sabrina, Lorenzon, Andrea, Sblattero, Daniele, Florian, Florella, Stebel, Marco, Marzari, Roberto, Not, Tarcisio, Aeschlimann, Daniel ORCID: https://orcid.org/0000-0003-0930-7706, 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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Abstract

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:	11 May 2023 19:52
URI:	https://orca.cardiff.ac.uk/id/eprint/15780

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