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Childhood coeliac disease: towards an improved serological mass screening strategy
C E Hogen Esch1, G D S Csizmadia, I M W van Hoogstraten
1Department of Paediatric Gastroenterology, Leiden University Medical Center, Leiden, The Netherlands. c.e.hogen_esch@lumc.nl
Insights
Optimizing coeliac disease (CD) screening in children by repeating antibody tests like EmA and tTGA can significantly reduce unnecessary biopsies. This approach improves diagnostic accuracy for asymptomatic young individuals.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Diagnostic Screening
Background:
- Mass screening for coeliac disease (CD) in asymptomatic children using anti-endomysium (EmA) testing identified a significant number of false positives.
- Of 57 seropositive children, 46% had normal histology upon biopsy, despite being HLA-DQ2/DQ8 positive, indicating a need to refine screening protocols.
Purpose of the Study:
- To enhance coeliac disease (CD) screening procedures in asymptomatic young children.
- To minimize the rate of unnecessary invasive biopsies following serological mass screening.
Main Methods:
- Comparison of various antibody tests including EmA, tissue-transglutaminase (tTGA), antigliadin, and deamidated-gliadin-peptides (anti-DGP).
- Optimization of test cut-off points and assessment of serological marker persistence (EmA, tTGA) over time.
Main Results:
- Tissue-transglutaminase (tTGA) and anti-DGP antibody levels correlated with EmA.
- Optimizing cut-off points reduced unnecessary biopsies by 50-96% but also decreased sensitivity.
- Antibody persistence differed: EmA in all CD vs. 50% non-CD; tTGA in 83% CD vs. 15% non-CD.
Conclusions:
- Transient coeliac disease (CD) antibodies can occur in genetically predisposed children.
- Repeating EmA and/or tTGA tests after 6 months in initially seropositive children can help avoid unnecessary biopsies.
- Improved serological screening protocols are crucial for reducing invasive procedures in pediatric CD diagnosis.
Background:
In 1997-1998, 6127 asymptomatic children aged 2-4 years were screened for coeliac disease (CD) by anti-endomysium (EmA) testing in the Netherlands. After 6 (+/-2) months, biopsies were performed in 57 seropositive children; 31(54%) had villous atrophy, but 26 (46%), all HLA-DQ2/DQ8 positive, had normal histology.
Aims:
To reduce the number of unnecessary biopsies after serological mass screening for CD in asymptomatic young children by optimizing screening procedures.
Methods:
Comparing different tests and optimizing their cut-off point: screening samples were tested for EmA, tissue-transglutaminase (tTGA), antigliadin and deamidated-gliadin-peptides (anti-DGP) antibodies. Determining serological persistence over time: persistence of EmA and tTGA was determined by testing serological samples obtained at biopsy.
Results:
Tissue-transglutaminase and anti-DGP correlated with EmA. Optimization of standard cut-off points not only reduced unnecessary biopsies by 50-96% but also reduced sensitivity. EmA persisted in all CD children, but in only 50% of the non-CD children. tTGA persisted in 83% of CD, but in only 15% of non-CD children.
Conclusions:
Coeliac disease antibodies may be present transiently in genetically predisposed children. To avoid unnecessary biopsies, serological mass screening procedures may be improved by repeating EmA and/or tTGA in initially seropositive young children after 6 months, before proceeding to biopsy. This may reduce the number of unnecessary biopsies that are performed.
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