{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:37:24Z","timestamp":1790735844437,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. pediatr. gastroenterol. nutr."],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives:<\/jats:title><jats:p>Production of autoantibodies to the enzyme tissue transglutaminase (tTG) is a hallmark of coeliac disease (CD). We have previously demonstrated that the immumoglobulin (Ig) A response to tTG in adult CD specifically targets its catalytic core region, containing the active\u2010site triad of amino acids. The aim of the present study was to investigate this phenomenon in paediatric patients with CD, and to elucidate the contribution of each active\u2010site residue to epitopes recognised. The specificity of the IgG anti\u2010tTG response was also investigated and compared with that of the IgA anti\u2010tTG response, in both paediatric and adult patients with CD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Wild\u2010type and novel variants of tTG were generated via site\u2010directed mutagenesis and expressed as glutathione\u2010S\u2010transferase\u2013fusion proteins in <jats:italic>Escherichia coli<\/jats:italic> BL\u201021. The mutagenic variants of tTG had substitutions of 1, 1, or all of the 3 of the catalytic triad amino acids. All of the recombinant tTGs were tested for their antigenicity in IgA and IgG enzyme\u2010linked immunosorbent assays with cohorts of paediatric (n = 63) and adult (n = 30) CD sera.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Substitution of even 1 amino acid in the catalytic triad resulted in a significant reduction of CD IgA and IgG anti\u2010tTG binding, with all of the mutant proteins displaying diminished antigenicity compared with the wild\u2010type protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>The core region of tTG is specifically targeted from early on in disease course by CD patient autoantibodies of both the IgA and IgG class.<\/jats:p><\/jats:sec>","DOI":"10.1097\/mpg.0b013e318251419f","type":"journal-article","created":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T09:17:13Z","timestamp":1330593433000},"page":"445-450","source":"Crossref","is-referenced-by-count":4,"title":["Binding of Autoantibodies 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