Anne Lammi1, Pekka Arikoski2, Arja Hakulinen3, Ursula Schwab4,5, Matti Uusitupa4, Seppo Heinonen6, Erkki Savilahti3, Tuure Kinnunen1, Jorma Ilonen1,7. 1. a 1 Department of Clinical Microbiology, University of Eastern Finland , Kuopio, Finland. 2. b 2 Department of Pediatrics, Kuopio University Hospital and University of Eastern Finland , Kuopio, Finland. 3. c 3 Children's Hospital, University of Helsinki , Helsinki, Finland. 4. d 4 Institute of Public Health and Clinical Nutrition, University of Eastern Finland , Kuopio, Finland. 5. e 5 Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital , Kuopio, Finland. 6. f 6 Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki , Helsinki, Finland. 7. g 7 Immunogenetics Laboratory, University of Turku , Turku, Finland.
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.
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.
Entities:
Keywords:
antibodies to deamidated gliadin peptide; celiac disease; children; gliadin-specific T cells; tissue transglutaminase antibodies