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  • Title: Binding of autoantibodies to the core region of tissue transglutaminase is a feature of paediatric coeliac disease.
    Author: Comerford R, Byrne G, Feighery C, Kelly J.
    Journal: J Pediatr Gastroenterol Nutr; 2012 Oct; 55(4):445-50. PubMed ID: 22383027.
    Abstract:
    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.
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