Optimization of serologic diagnosis of celiac disease in the pediatric setting
Open accessAbstract
BACKGROUND The clinical presentation of celiac disease (CD) varies between children. The objective of this study was to document the pre-test probability for CD based on symptoms and routine laboratory test and to evaluate the performance of two IgA anti-tissue transglutaminase (tTG) assays. We critically reviewed the concept of using multiples of the manufacturer's upper limit of normal (ULN), as proposed in the ESPGHAN guidelines (if IgA tTG is >10 times ULN, no biopsy is needed). METHODS The retrospective study included 91 children with newly diagnosed CD and 605 controls (<16 years). All underwent upper endoscopy with small bowel biopsies. Four laboratory parameters and 16 symptoms were registered. All patients were tested for IgA anti-tTG antibodies with assays from Inova Diagnostics and Thermo Fisher Scientific. RESULTS Some combinations of clinical symptoms and laboratory parameters had a high pre-test probability for CD, such as (combinations of) anorexia, failure to thrive, low ferritin level and elevated AST. The diagnostic performance of both IgA anti-tTG assays was excellent and comparable (no difference in ROC curve area under the curve). At a threshold that corresponds to a specificity of 100% (5 times ULN for Inova Diagnostics and 2 times ULN for Thermo Fisher), the sensitivity was 82% for both assays. At the 10 times ULN threshold, the sensitivity differed between the assays (77% vs. 57%), indicating that such threshold does not completely align interpretation across companies. CONCLUSIONS Our study showed that some combinations of symptoms and aberrant laboratory parameters had a high pre-test probability. The use of the ESPGHAN non-biopsy approach could reduce small bowel biopsies, but thresholds for IgA-tTG levels are not aligned across assays and should be based on predefined likelihood ratios or specificity.
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Test result (or test result interval) specific likelihood ratios have already been applied for other autoantibodies (e.g. anti-MPO and anti-PR3 antibodies, anti-nuclear autoantibodies and anti-tissue transglutaminase antibodies).
“This has already been applied for other autoantibodies (e.g. anti-MPO and anti-PR3 antibodies, anti-nuclear autoantibodies and anti-tissue transglutaminase antibodies) [85], [86], [87]”
From Laboratory evaluation of anti-dsDNA antibodies. (2022) · cites this paper as [85]
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- Authors
- Bogaert, L., Cauchie, M., Van Hoovels, L., Vermeersch, P., Fierz, W., De Hertogh, G., Hoffman, I., & Bossuyt, X.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- Europe Hospitals (BE)
- Corresponding author
- Bossuyt, Xavier
- Venue
- Autoimmunity Reviews
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 19
- Issue
- 5
- Pages
- 102513
- ISSN
- 1568-9972 (ISSN-L)
- OpenAlex
- W3011641169
- Semantic Scholar
- ef98ea54249fbc29214369bccd6ba4f3c1fc2d46
- Cited by
- 17
- References
- 33
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 1 · 2021: 2 · 2020: 4
- FWCI
- 2.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autoimmunity Reviews (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Funders
- Scientific Research – Flanders
- Topics
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Health Sciences › Medicine › Surgery › Eosinophilic Esophagitis
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Wheat and Barley Genetics and Pathology
- Keywords
- celiac disease, serological diagnosis, pretest probability, ESPGHAN guidelines, non-biopsy diagnosis, small bowel biopsy, sensitivity and specificity, pediatric celiac disease, failure to thrive, anorexia, ferritin, aspartate aminotransferase
- MeSH terms
- Adolescent, Autoantibodies, Biopsy, Celiac Disease, Child, Child, Preschool, Female, Humans, Immunoglobulin A, Infant, Infant, Newborn, Male, Transglutaminases, Retrospective Studies, Sensitivity and Specificity
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