Antibodies against neo-epitope of microbial and human transglutaminase complexes as biomarkers of childhood celiac disease

Research output: Contribution to journalArticle

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), 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.

Details

Authors
  • D. Agardh
  • T. Matthias
  • P. Wusterhausen
  • S. Neidhöfer
  • A. Heller
  • A. Lerner
Organisations
External organisations
  • Skåne University Hospital
  • AESKU.KIPP Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
  • Pediatrics

Keywords

  • antibodies, autoantibodies, celiac disease, diagnosis, human tissue transglutaminase, microbial transglutaminase, serological markers
Original languageEnglish
JournalClinical and Experimental Immunology
Publication statusE-pub ahead of print - 2019 Oct 30
Publication categoryResearch
Peer-reviewedYes