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

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Lammi , A , Arikoski , P , Hakulinen , A , Schwab , U , Uusitupa , M , Heinonen , S , Savilahti , E , Kinnunen , T & Ilonen , J 2016 , ' Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease ' Scandinavian Journal of Gastroenterology , vol. 51 , no. 2 , pp. 168-177 . DOI: 10.3109/00365521.2015.1067328

Title: Development of gliadin-specific immune responses in children with HLA-associated genetic risk for celiac disease
Author: Lammi, Anne; Arikoski, Pekka; Hakulinen, Arja; Schwab, Ursula; Uusitupa, Matti; Heinonen, Seppo; Savilahti, Erkki; Kinnunen, Tuure; Ilonen, Jorma
Contributor: University of Helsinki, Clinicum
University of Helsinki, Department of Obstetrics and Gynegology
University of Helsinki, Children's Hospital
Date: 2016-02-01
Language: eng
Number of pages: 10
Belongs to series: Scandinavian Journal of Gastroenterology
ISSN: 0036-5521
URI: http://hdl.handle.net/10138/161411
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.
Subject: children
tissue transglutaminase antibodies
gliadin-specific T cells
antibodies to deamidated gliadin peptide
celiac disease
DEAMIDATED GLIADIN
T-CELLS
PERIPHERAL-BLOOD
GLUTEN CHALLENGE
NATURAL-HISTORY
ANTIBODIES
TRANSGLUTAMINASE
SUSCEPTIBILITY
PREVALENCE
DIAGNOSIS
3121 Internal medicine
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