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Journal of Pediatric Gastroenterology & Nutrition:
doi: 10.1097/MPG.0b013e318251419f

Binding of Autoantibodies to the Core Region of Tissue Transglutaminase Is a Feature of Paediatric Coeliac Disease

Comerford, Ross*; Byrne, Greg; Feighery, Conleth; Kelly, Jacinta*

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Objectives: 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-site 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-site residue to epitopes recognised. The specificity of the IgG anti-tTG response was also investigated and compared with that of the IgA anti-tTG response, in both paediatric and adult patients with CD.

Methods: Wild-type and novel variants of tTG were generated via site-directed mutagenesis and expressed as glutathione-S-transferase–fusion proteins in Escherichia coli BL-21. 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-linked immunosorbent assays with cohorts of paediatric (n = 63) and adult (n = 30) CD sera.

Results: Substitution of even 1 amino acid in the catalytic triad resulted in a significant reduction of CD IgA and IgG anti-tTG binding, with all of the mutant proteins displaying diminished antigenicity compared with the wild-type protein.

Conclusions: 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.

Copyright 2012 by ESPGHAN and NASPGHAN


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