Longitudinal screening of HLA‐risk and HLA‐nonrisk children for celiac disease to age 15 years: CiPiS study

Abstract

AbstractObjectivesAutoantibodies against tissue transglutaminase (tTG) are serological markers of celiac disease. The aim was to study the applicability of human leukocyte antigen (HLA)‐genotyping and tTG autoantibodies in the screening of celiac disease in a longitudinal birth cohort followed to age 15 years.MethodsIncluded were 13,860 HLA‐DQ‐genotyped children at birth and previously invited to a screening at age 3 and 9 years, respectively. HLA‐DQB1*02 and/or DQB1*03:02 (HLA‐risk) children were compared with non‐HLA‐DQB1*02 and non‐DQB1*03:02 (HLA‐nonrisk) children. The present study reinvited 12,948/13,860 (93.4%) children at age 15 years of whom 1056/2374 (44.5%) participated in screening at both age 3 and 9 years. Both immunoglobulin A (IgA) and G (IgG) autoantibodies against tTG were analyzed separately in radiobinding assays. Persistently tTG autoantibody‐positive children were examined with intestinal biopsy to confirm the diagnosis of celiac disease.ResultsAt age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA‐risk children compared with 0/1824 HLA‐nonrisk children (p < 0.001). By age 9 years, celiac disease was diagnosed in 72/1910 (3.8%) HLA‐risk children compared with 0/2167 HLA‐nonrisk children (p < 0.001). Screening at age 15 years detected 14/1071 (1.3%) HLA‐risk children positive for IgA‐tTG and/or IgG‐tTG of whom 12/1071 (1.1%) remained persistently positive. Among those, 10/1071 (0.9%, 95% confidence interval: 0.4%–1.7%) HLA‐risk children were diagnosed with celiac disease compared with 0/1303 HLA‐nonrisk children (p < 0.001) and 5/491 (1.0%) were negative in screenings at both 3 and 9 years of age.ConclusionsScreening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA‐risk.