The industrial food additive microbial transglutaminase, mimics the tissue transglutaminase and is immunogenic in celiac disease patients

Publication date: Available online 15 September 2016
Source:Autoimmunity Reviews
Author(s): T. Matthias, P. Jeremias, S. Neidhöfer, A. Lerner
Microbial transglutaminase (mTg) is capable of cross-linking numerous molecules. It is a family member of human tissue transglutaminase (tTg), involved in CD. Despite declarations of mTg industrial use safety, direct evidence for immunogenicity of the enzyme is lacking.The serological activity of mTg, tTg, gliadin complexed mTg (mTg neo-epitope) and gliadin complexed tTg (tTg neo-epitope) were studied in: 95 pediatric celiac patients (CD), 99 normal children (NC) 79 normal adults (NA) and 45 children with nonspecific abdominal pain (AP). Sera were tested by ELISAs, detecting IgA, IgG or both IgA and IgG (check): AESKULISA® tTg (tTg), AESKULISA® tTg New Generation (tTg neo-epitope (tTg-neo)), microbial transglutaminase (mTg) and mTg neo-epitope (mTg-neo). Marsh criteria were used for the degree of intestinal injury. Parallel, mTg and tTg neo-epitopes were purified by asymmetric field flow fractionation, confirmed by multi light scattering and SDS-page, and analyzed on the adult CD and controls group by competition ELISAs.No sequence homology but active site similarity were detected on alignment of the 2 Tgs. Comparing pediatric CD patients with the 2 normal groups: mTg-neo IgA, IgG and IgA+IgG antibody activities exceed the comparable mTg ones (p<0.0001). All mTg-neo and tTg-neo levels were higher (p<0.001). tTg IgA and IgG+IgA were higher than mTg IgA and IgA+IgG (p<0.0001). The levels of tTg-neo IgA/IgG were higher than tTg IgA/IgG (p<0.0001). The sequential antibody activities reflecting best the increased intestinal damage were: tTg-neo check>tTg-neo IgA≥mTg-neo IgG>tTg-neo IgG>mTg-neo check > mTg-neo IgA. Taken together, tTg-neo check, tTg-neo IgA and mTg-neo IgG correlated best with intestinal pathology (r²=0.6454, r²=0.6165,r²=0.5633 p<0.0001, p<0.0001, p<0.0001, respectively). Purified mTg-neo IgG and IgA showed an increased immunoreactivity compared to single mTg and gliadin (p<0.001) but similar immunoreactivity to the tTg-neo IgG and IgA ELISA. Using a competition ELISA, the mTg neo-epitopes and tTg neo-epitopes have identical outcomes in CD sera both showing a decrease in optical density of 55±6%, (p<0.0002).mTg is immunogenic in children with CD and by complexing to gliadin its immunogenicity is enhanced. Anti-mTg-neo-epitope IgG antibodies correlate with intestinal damage to a comparable degree as anti-tTg-neo IgA. mTg and tTg display a comparable immunopotent epitope. mTg-neo IgG is a new marker for CD. Further studies are needed to explore the pathogenic potential of anti-mTg antibodies in CD.



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