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

Boström, Michaela LU ; Brundin, Charlotte LU ; Björck, Sara LU and Agardh, Daniel LU (2024) In Journal of Pediatric Gastroenterology and Nutrition - Jpgn 78(5). p.1143-1148
Abstract
Objectives
Autoantibodies 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.

Methods
Included 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... (More)
Objectives
Autoantibodies 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.

Methods
Included 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.

Results
At 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.

Conclusions
Screening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA-risk.

Highlights
What is Known
Celiac disease (CD) is often clinically silent and could be difficult to detect.

Tissue transglutaminase autoantibodies are serological markers of CD and can be used in screenings.

What is New
Screening for CD can be restricted to HLA at-risk individuals.

Most cases of screening-detected CD are detected during the first decade of life. (Less)
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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Pediatric Gastroenterology and Nutrition - Jpgn
volume
78
issue
5
pages
1143 - 1148
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85188126196
ISSN
1536-4801
DOI
10.1002/jpn3.12181
language
English
LU publication?
yes
id
4fdbf5df-72db-4c6e-916e-857f0fc20073
date added to LUP
2026-04-27 10:19:45
date last changed
2026-04-28 04:00:50
@article{4fdbf5df-72db-4c6e-916e-857f0fc20073,
  abstract     = {{Objectives<br/>Autoantibodies 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.<br/><br/>Methods<br/>Included 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.<br/><br/>Results<br/>At age 3 years, celiac disease was diagnosed in 56/1635 (3.4%) HLA-risk children compared with 0/1824 HLA-nonrisk children (p &lt; 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 &lt; 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 &lt; 0.001) and 5/491 (1.0%) were negative in screenings at both 3 and 9 years of age.<br/><br/>Conclusions<br/>Screening for celiac disease needs to be performed at multiple timepoints to detect all cases but can be restricted to children at HLA-risk.<br/><br/>Highlights<br/>What is Known<br/>Celiac disease (CD) is often clinically silent and could be difficult to detect.<br/><br/>Tissue transglutaminase autoantibodies are serological markers of CD and can be used in screenings.<br/><br/>What is New<br/>Screening for CD can be restricted to HLA at-risk individuals.<br/><br/>Most cases of screening-detected CD are detected during the first decade of life.}},
  author       = {{Boström, Michaela and Brundin, Charlotte and Björck, Sara and Agardh, Daniel}},
  issn         = {{1536-4801}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1143--1148}},
  publisher    = {{Lippincott Williams & Wilkins}},
  series       = {{Journal of Pediatric Gastroenterology and Nutrition - Jpgn}},
  title        = {{Longitudinal screening of HLA-risk and HLA-nonrisk children for celiac disease to age 15 years: CiPiS study}},
  url          = {{http://dx.doi.org/10.1002/jpn3.12181}},
  doi          = {{10.1002/jpn3.12181}},
  volume       = {{78}},
  year         = {{2024}},
}