Anti transglutaminase antibodies cause ataxia in mice

• Published in: PloS one 2010-03, Vol.5 (3), p.e9698-e9698
• Main Authors: Boscolo, Sabrina, Lorenzon, Andrea, Sblattero, Daniele, Florian, Fiorella, Stebel, Marco, Marzari, Roberto, Not, Tarcisio, Aeschlimann, Daniel, Ventura, Alessandro, Hadjivassiliou, Marios, Tongiorgi, Enrico
• Format: Article
• Language: English
• Subjects: Adult; Analysis; Angiogenesis; Animals; Antibodies; Antibodies - chemistry; Antibody libraries; Antigen-antibody reactions; Antigens; Ataxia; Ataxia - etiology; Ataxia - immunology; Autoimmune diseases; Autoimmune Diseases - immunology; Biotechnology; Blood vessels; Brain; Brain - pathology; Celiac disease; Celiac Disease - immunology; Cloning; Disease; Enzyme-linked immunosorbent assay; Female; Gastrointestinal diseases; Gliadin; Gliadin - chemistry; Gluten; Haplotypes; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulins; Immunohistochemistry; Immunology/Autoimmunity; Isoenzymes; Libraries; Life sciences; Localization; Male; Medical research; Mice; Mice, Inbred C57BL; Middle Aged; Motor Skills; Neurological diseases; Neurological Disorders/Movement Disorders; Neuronal-glial interactions; Neurons; Patients; Phages; Rats; Rats, Sprague-Dawley; Transglutaminase 2; Transglutaminases - immunology; Veins & arteries
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009698

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