Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease
: Anne Lammi, Pekka Arikoski, Arja Hakulinen, Ursula Schwab, Matti Uusitupa, Seppo Heinonen, Erkki Savilahti, Tuure Kinnunen, Jorma Ilonen
Publisher: Taylor and Francis Ltd
: 2016
Scandinavian Journal of Gastroenterology
Scandinavian Journal of Gastroenterology
: 51
: 2
: 168
: 177
: 10
: 0036-5521
: 1502-7708
DOI: https://doi.org/10.3109/00365521.2015.1067328
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.