Changes in Non-Deamidated versus Deamidated Epitope Targeting and Disease Prediction during the Antibody Response to Gliadin and Transglutaminase of Infants at Risk for Celiac Disease

Ádám Diós, Bharani Srinivasan, Judit Gyimesi, Katharina Werkstetter, Rudolf Valenta, Sibylle Koletzko, Ilma R Korponay-Szabó

Research output: Journal article (peer-reviewed)Journal article

Abstract

Celiac disease (CeD) is a conditional autoimmune disorder with T cell-mediated immune response to gluten coupled with antibody production to gliadin and the self-protein tissue transglutaminase (TG2). TG2 contributes to the CeD pathomechanism by deamidating gliadin, thereby generating more immunogenic peptides. Anti-gliadin antibodies may appear before the autoantibody production. The scope of this study was to dissect these early antibody responses by investigating serum samples collected during the PreventCD prospective double-blind study, where infants with high CeD risk were randomized to 200 mg daily gluten intake or placebo from 4 to 6 months of age, followed by frequent blood testing on regular gluten consumption in both groups. After primary gluten intake, children with or without later CeD produced IgA and IgG antibodies which preferentially recognized non-deamidated gliadin peptides. At CeD development with anti-TG2 seroconversion, there was a significant increase in the antibody reaction toward deamidated gliadin peptides (DGP), with maturation in the binding strength for the PEQPFP gamma-gliadin core peptide. The earliest produced autoantibodies targeted TG2's celiac epitope 2. Our results reveal a qualitative change in the gliadin-directed humoral immune response at the time when anti-TG2 antibodies appear, but anti-DGP antibodies in the absence of anti-TG2 antibodies are not disease-predictive.

Original languageEnglish
Article number2498
JournalInternational Journal of Molecular Sciences
Volume23
Issue number5
DOIs
Publication statusPublished - 1 Mar 2022

Keywords

  • Antibody Formation
  • Autoantibodies
  • Celiac Disease
  • Child
  • Epitopes
  • Gliadin
  • Glutens
  • Humans
  • Immunoglobulin A
  • Infant
  • Peptides
  • Prospective Studies
  • Transglutaminases/metabolism

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