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Characterization of the Anti-Tissue Transglutaminase Antibody Response in Nonobese Diabetic Mice¹

Daniele Sblattero^2,*, Francesco Maurano, Giuseppe Mazzarella, Mauro Rossi, Salvatore Auricchio, Fiorella Florian^*, Fabiana Ziberna, Alberto Tommasini, Tarcisio Not, Alessandro Ventura, Andrew Bradbury^¶, Roberto Marzari^* and Riccardo Troncone^,

^* Department of Biology, University of Trieste, Trieste, Italy; Institute of Food Science and Technology, Consiglio Nazionale delle Ricerche (CNR), Avellino, Italy; Department of Paediatrics and European Laboratory for the Investigation of Food Induced Diseases, University Federico II, Naples, Italy; Department of Sciences of Reproduction and Development, University of Trieste and Istituto di Riconero e Cura a Carattere Scientifico "Burlo Garofolo", Trieste, Italy; and ^¶ Biosciences Division, Los Alamos National Laboratory, Los Alamos, NM

Type 1 diabetes mellitus is an autoimmune disorder characterized by destruction of insulin-producing pancreatic cells by T lymphocytes. In nonobese diabetic (NOD) mice, a role has been hypothesized for dietary gluten proteins in the onset of diabetes, and because gluten dependence is the major feature of celiac disease, together with production of Abs to the autoantigen tissue transglutaminase (tTG), we looked for the presence of anti-tTG Abs in the serum of NOD mice and, to establish their origin, analyzed the Ab repertoire of NOD mice using phage display Ab libraries. We found significant levels of serum anti-tTG Abs and were able to isolate single-chain Ab fragments to mouse tTG mainly from the Ab libraries made from intestinal lymphocytes and to a lesser extent from splenocytes. Data from NOD mice on a gluten-free diet suggest that the anti-tTG response is not gluten-dependent. The intestinal Ab response to tTG is a feature of NOD mice, but the underlying mechanisms remain obscure.