Antibodies against neo-epitope of microbial and human transglutaminase complexes as biomarkers of childhood celiac disease
(2020) In Clinical and Experimental Immunology 199(3). p.294-302- Abstract
Tissue transglutaminase (tTG) and microbial transglutaminase (mTG) cross-link gliadins to form complexes that expose immunogenic neo-epitopes to produce tTG and mTG-neo-epitope antibodies. The aim of this study was to test the diagnostic performance of antibodies against non-complexed and complexed forms of transglutaminases, to correlate their activities to the intestinal damage and to explore age group dependency in celiac disease (CD). A total of 296 children with untreated CD and 215 non-celiac disease controls were checked by in-house enzyme-linked immunosorbent assays detecting immunoglobulin (Ig)A, IgG or combined detection of IgA and IgG (check) against tTG, AESKULISA® tTG New Generation (tTG-neo) and mTG-neo (RUO),... (More)
Tissue transglutaminase (tTG) and microbial transglutaminase (mTG) cross-link gliadins to form complexes that expose immunogenic neo-epitopes to produce tTG and mTG-neo-epitope antibodies. The aim of this study was to test the diagnostic performance of antibodies against non-complexed and complexed forms of transglutaminases, to correlate their activities to the intestinal damage and to explore age group dependency in celiac disease (CD). A total of 296 children with untreated CD and 215 non-celiac disease controls were checked by in-house enzyme-linked immunosorbent assays detecting immunoglobulin (Ig)A, IgG or combined detection of IgA and IgG (check) against tTG, AESKULISA® tTG New Generation (tTG-neo) and mTG-neo (RUO), IgA and IgG antibodies against deamidated gliadin peptide (DGP) and human IgA anti-endomysium antibodies (EMA) using AESKUSLIDES® EMA. Intestinal pathology was graded according the revised Marsh criteria, and age dependencies of the antibody activities were analysed. Using cut-offs estimated from receiver operating characteristic (ROC) curves, the highest area under curve (AUC) of the TG assays was 0·963 for tTG-neo check, followed by tTG check (0·962) when the diagnosis was based on enteric mucosal histology. tTG-neo check was the most effective to reflect the intestinal abnormalities in CD (r = 0·795, P < 0·0001). High levels of anti-mTG-neo IgG and anti-tTG-neo IgG appeared in the earlier age groups, as compared to anti-tTG IgG (P < 0·001). Considering antibody diagnostic performance based on AUC, enteric damage reflection and predictability at an early age, the anti-neo tTG check was the most effective diagnostic biomarker for pediatric CD. The mTG neo check might represent a new marker for CD screening, diagnosis and predictability.
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- author
- Agardh, D. LU ; Matthias, T. ; Wusterhausen, P. ; Neidhöfer, S. ; Heller, A. and Lerner, A.
- organization
- publishing date
- 2020-03
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- antibodies, autoantibodies, celiac disease, diagnosis, human tissue transglutaminase, microbial transglutaminase, serological markers
- in
- Clinical and Experimental Immunology
- volume
- 199
- issue
- 3
- pages
- 9 pages
- publisher
- British Society for Immunology
- external identifiers
-
- scopus:85074976910
- pmid:31663117
- ISSN
- 0009-9104
- DOI
- 10.1111/cei.13394
- language
- English
- LU publication?
- yes
- id
- c283a1bf-b435-4ac9-bef3-d6d4f5a551f3
- date added to LUP
- 2019-12-03 09:40:53
- date last changed
- 2021-02-17 05:17:41
@article{c283a1bf-b435-4ac9-bef3-d6d4f5a551f3,
abstract = {<p>Tissue transglutaminase (tTG) and microbial transglutaminase (mTG) cross-link gliadins to form complexes that expose immunogenic neo-epitopes to produce tTG and mTG-neo-epitope antibodies. The aim of this study was to test the diagnostic performance of antibodies against non-complexed and complexed forms of transglutaminases, to correlate their activities to the intestinal damage and to explore age group dependency in celiac disease (CD). A total of 296 children with untreated CD and 215 non-celiac disease controls were checked by in-house enzyme-linked immunosorbent assays detecting immunoglobulin (Ig)A, IgG or combined detection of IgA and IgG (check) against tTG, AESKULISA<sup>®</sup> tTG New Generation (tTG-neo) and mTG-neo (RUO), IgA and IgG antibodies against deamidated gliadin peptide (DGP) and human IgA anti-endomysium antibodies (EMA) using AESKUSLIDES<sup>®</sup> EMA. Intestinal pathology was graded according the revised Marsh criteria, and age dependencies of the antibody activities were analysed. Using cut-offs estimated from receiver operating characteristic (ROC) curves, the highest area under curve (AUC) of the TG assays was 0·963 for tTG-neo check, followed by tTG check (0·962) when the diagnosis was based on enteric mucosal histology. tTG-neo check was the most effective to reflect the intestinal abnormalities in CD (r = 0·795, P < 0·0001). High levels of anti-mTG-neo IgG and anti-tTG-neo IgG appeared in the earlier age groups, as compared to anti-tTG IgG (P < 0·001). Considering antibody diagnostic performance based on AUC, enteric damage reflection and predictability at an early age, the anti-neo tTG check was the most effective diagnostic biomarker for pediatric CD. The mTG neo check might represent a new marker for CD screening, diagnosis and predictability.</p>},
author = {Agardh, D. and Matthias, T. and Wusterhausen, P. and Neidhöfer, S. and Heller, A. and Lerner, A.},
issn = {0009-9104},
language = {eng},
number = {3},
pages = {294--302},
publisher = {British Society for Immunology},
series = {Clinical and Experimental Immunology},
title = {Antibodies against neo-epitope of microbial and human transglutaminase complexes as biomarkers of childhood celiac disease},
url = {http://dx.doi.org/10.1111/cei.13394},
doi = {10.1111/cei.13394},
volume = {199},
year = {2020},
}