Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease

Scand J Gastroenterol. 2016;51(2):168-77. doi: 10.3109/00365521.2015.1067328. Epub 2015 Jul 10.

Abstract

Objective: The development of gliadin-specific antibody and T-cell responses were longitudinally monitored in young children with genetic risk for celiac disease (CD).

Material and methods: 291 newborn children positive for HLA-DQB1*02 and -DQA1*05 alleles were followed until 3-4 years of age by screening for tissue transglutaminase autoantibodies (tTGA) by using a commercial ELISA-based kit and antibodies to deamidated gliadin peptide (anti-DGP) by an immunofluorometric assay. Eighty-five of the children were also followed for peripheral blood gliadin-specific CD4(+) T-cell responses by using a carboxyfluorescein diacetate succinimidyl ester-based in vitro proliferation assay.

Results: The cumulative incidence of tTGA seropositivity during the follow-up was 6.5%. CD was diagnosed in nine of the tTGA-positive children (3.1%) by duodenal biopsy at a median 3.5 years of age. All of the children with confirmed CD were both IgA and IgG anti-DGP positive at the time of tTGA seroconversion and in over half of the cases IgG anti-DGP positivity even preceded tTGA seroconversion. Peripheral blood T-cell responses to deamidated and native gliadin were detected in 40.5% and 22.2% of the children at the age of 9 months and these frequencies decreased during the follow-up to the levels of 22.2% and 8.9%, respectively.

Conclusions: Anti-DGP antibodies may precede tTGA seroconversion and thus frequent monitoring of both tTGA and anti-DGP antibodies may allow earlier detection of CD in genetically susceptible children. Peripheral blood gliadin-specific T-cell responses are relatively common in HLA-DQ2-positive children and are not directly associated with the development of CD.

Keywords: antibodies to deamidated gliadin peptide; celiac disease; children; gliadin-specific T cells; tissue transglutaminase antibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood*
  • CD4-Positive T-Lymphocytes / immunology
  • Celiac Disease / genetics*
  • Celiac Disease / immunology*
  • Celiac Disease / pathology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Child, Preschool
  • Female
  • GTP-Binding Proteins / immunology*
  • Gliadin / immunology*
  • Gliadin / pharmacology
  • HLA-DQ alpha-Chains / genetics
  • HLA-DQ beta-Chains / genetics
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases / immunology*

Substances

  • Autoantibodies
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • Immunoglobulin A
  • Immunoglobulin G
  • Gliadin
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins