title: 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).
  
  
  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.
authors.affiliation: a 1 Department of Clinical Microbiology, University of Eastern Finland , Kuopio, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Lammi
authors.affiliation: b 2 Department of Pediatrics, Kuopio University Hospital and University of Eastern Finland , Kuopio, Finland.
authors.forename: Pekka
authors.initials: P
authors.lastname: Arikoski
authors.affiliation: c 3 Children's Hospital, University of Helsinki , Helsinki, Finland.
authors.forename: Arja
authors.initials: A
authors.lastname: Hakulinen
authors.affiliation: d 4 Institute of Public Health and Clinical Nutrition, University of Eastern Finland , Kuopio, Finland.|e 5 Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital , Kuopio, Finland.
authors.forename: Ursula
authors.initials: U
authors.lastname: Schwab
authors.affiliation: d 4 Institute of Public Health and Clinical Nutrition, University of Eastern Finland , Kuopio, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Uusitupa
authors.affiliation: f 6 Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki , Helsinki, Finland.
authors.forename: Seppo
authors.initials: S
authors.lastname: Heinonen
authors.affiliation: c 3 Children's Hospital, University of Helsinki , Helsinki, Finland.
authors.forename: Erkki
authors.initials: E
authors.lastname: Savilahti
authors.affiliation: a 1 Department of Clinical Microbiology, University of Eastern Finland , Kuopio, Finland.
authors.forename: Tuure
authors.initials: T
authors.lastname: Kinnunen
authors.affiliation: a 1 Department of Clinical Microbiology, University of Eastern Finland , Kuopio, Finland.|g 7 Immunogenetics Laboratory, University of Turku , Turku, Finland.
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D005903:Gliadin / Q000276:immunology* / Q000494:pharmacology; D059848:HLA-DQ alpha-Chains / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: antibodies to deamidated gliadin peptide; celiac disease; children; gliadin-specific T cells; tissue transglutaminase antibodies