title: Repeated Screening Can Be Restricted to At-Genetic-Risk Birth Cohorts.
abstract: OBJECTIVE
  Celiac disease (CD) is associated with tissue transglutaminase autoantibodies (tTGAs) in individuals carrying the human leukocyte antigen (HLA) risk haplotypes DQA1*05:01-DQB1*02:01 (DQ2) and/or DQA1*03:01-DQB1*03:02 (DQ8). The aim of the study was to identify CD in an HLA-genotyped birth cohort prospectively screened for CD.
  
  
  METHODS
  In the initial screening, 13,860 HLA-DQ-genotyped children were invited, of whom 3435/13,860 (25%) accepted participation. Of the 3435, 1620 (47%) carried DQ2 and/or DQ8, of whom 73 (4.5%) were tTGA positive assessed in radioligand-binding assays and 56 (3.5%) developed CD. At age 9 years, 13,024 children from the original cohort were re-invited to follow-up screening using the same study protocol and tTGA assays as in the first screening. Diagnosis of CD was confirmed by intestinal biopsy in children with persistent tTGA.
  
  
  RESULTS
  In the follow-up screening, 1910/4077 (46.8%) carried DQ2 and/or DQ8, of whom 79/1910 (4.1%) were persistently tTGA positive and 72/1907 (3.8%) developed CD. Only 1/2167 (0.05%) child without HLA risk was IgG-tTGA positive, but did not have CD. Of the 980/1910 (51%) children carrying DQ2 and/or DQ8 who were already screened at 3 years of age, 30/979 (3.1%) were diagnosed as new patients at 9 years of age, compared with 42/928 (4.5%) children who did not participate in the initial screening (P = 0.094).
  
  
  CONCLUSIONS
  Screening for CD can be restricted to children carrying HLA-DQ2 and/or DQ8. Repeated screening using tTGA is necessary to identify new patients by 9 years of age. These findings may be relevant when considering implementing screening of the general population.
authors: *Unit of Diabetes and Celiac Disease, Department of Clinical Sciences, Lund University, Malmö, Sweden †Health Informatics Institute, University of South Florida, Tampa.
authors: Sara
authors: S
authors: Björck
authors: Kristian
authors: K
authors: Lynch
authors: Charlotte
authors: C
authors: Brundin
authors: Daniel
authors: D
authors: Agardh
mesh_terms: D001323:Autoantibodies / Q000378:metabolism*; D001327:Autoimmune Diseases; D001706:Biopsy; D002446:Celiac Disease / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D019204:GTP-Binding Proteins / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008403:Mass Screening; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012307:Risk Factors; D011503:Transglutaminases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins