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

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.

Key Words:

• antibodies to deamidated gliadin peptide
• celiac disease
• children
• gliadin-specific T cells
• tissue transglutaminase antibodies

Acknowledgements

The authors thank Anne Björk and Sirpa Nolvi for carrying out the recruitment as well as the organization of sample collection with the participating families. The authors also thank Virpi Fisk and Terttu Laurén for excellent technical assistance. This study was financially supported by grants from the Finnish Coeliac Society, The Finnish-Norwegian Medical Foundation, The Finnish Cultural Foundation, Päivikki and Sakari Sohlberg Foundation, Finland and Special Research Funds for Kuopio University Hospital.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.