AGA Clinical Practice Update on Diagnosis and Monitoring of Celiac Disease—Changing Utility of Serology and Histologic Measures: Expert Review
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Purpose The purpose of this clinical practice update is to define key modalities in the diagnosis and monitoring of celiac disease (CD) in adults as well as in children and adolescents. Methods The recommendations outlined in this expert review are based on available published evidence, including cohort and case-control studies of the diagnostic process as well as controlled and descriptive studies of disease management. Best Practice Advice 1: Serology is a crucial component of the detection and diagnosis of CD, particularly tissue transglutaminase-immunoglobulin A (TG2-IgA), IgA testing, and less frequently, endomysial IgA testing. Best Practice Advice 2: Thorough histological analysis of duodenal biopsies with Marsh classification, counting of lymphocytes per high-power field, and morphometry is important for diagnosis as well as for differential diagnosis. Best Practice Advice 2a: TG2-IgA, at high levels (> ×10 upper normal limit) is a reliable and accurate test for diagnosing active CD. When such a strongly positive TG2-IgA is combined with a positive endomysial antibody in a second blood sample, the positive predictive value for CD is virtually 100%. In adults, esophagogastroduodenoscopy (EGD) and duodenal biopsies may then be performed for purposes of differential diagnosis. Best Practice Advice 3: IgA deficiency is an infrequent but important explanation for why patients with CD may be negative on IgA isotype testing despite strong suspicion. Measuring total IgA levels, IgG deamidated gliadin antibody tests, and TG2-IgG testing in that circumstance is recommended. Best Practice Advice 4: IgG isotype testing for TG2 antibody is not specific in the absence of IgA deficiency. Best Practice Advice 5: In patients found to have CD first by intestinal biopsies, celiac-specific serology should be undertaken as a confirmatory test before initiation of a gluten-free diet (GFD). Best Practice Advice 6: In patients in whom CD is strongly suspected in the face of negative biopsies, TG2-IgA should still be performed and, if positive, repeat biopsies might be considered either at that time or sometime in the future. Best Practice Advice 7: Reduction or avoidance of gluten before diagnostic testing is discouraged, as it may reduce the sensitivity of both serology and biopsy testing. Best Practice Advice 8: When patients have already started on a GFD before diagnosis, we suggest that the patient go back on a normal diet with 3 slices of wheat bread daily preferably for 1 to 3 months before repeat determination of TG2-IgA. Best Practice Advice 9: Determination of HLA-DQ2/DQ8 has a limited role in the diagnosis of CD. Its value is largely related to its negative predictive value to rule out CD in patients who are seronegative in the face of histologic changes, in patients who did not have serologic confirmation at the time of diagnosis, and in those patients with a historic diagnosis of CD; especially as very young children before the introduction of celiac-specific serology. Management Best Practice Advice 10: Celiac serology has a guarded role in the detection of continued intestinal injury, in particular as to sensitivity, as negative serology in a treated patient does not guarantee that the intestinal mucosa has healed. Persistently positive serology usually indicates ongoing intestinal damage and gluten exposure. Follow-up serology should be performed 6 and 12 months after diagnosis, and yearly thereafter. Best Practice Advice 11: Patients with persistent or relapsing symptoms, without other obvious explanations for those symptoms, should undergo endoscopic biopsies to determine healing even in the presence of negative TG2-IgA.
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Normalization of serology is widely used during follow-up as a proxy for mucosal healing in children with high positive and negative predictive values.
“Normalization of serology is widely used during follow-up as a proxy for mucosal healing in children with high positive and negative predictive values (21-23).”
From ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. (2022) · cites this paper as [23]
The Management and Follow-up section (page not provided) says follow-up serology is more useful in children than adults and reports a higher negative predictive value. It also describes the positive predictive value of persistently positive TG2-IgA as fairly low. Best Practice Advice 10 (page not provided) cautions that negative serology does not guarantee mucosal healing, so the claim of high positive and negative predictive values overstates the source. (LLM, conf=0.88)
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Self-citation
- Authors
- Husby, S., Murray, J. A., & Katzka, D. A.
- Affiliations
- Odense University Hospital (DK)
- Mayo Clinic (US)
- Corresponding author
- Murray, Joseph A.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 156
- Issue
- 4
- Pages
- 885-889
- ISSN
- 0016-5085 (ISSN-L)
- PMC
- PMC6409202
- OpenAlex
- W2904016703
- Cited by
- 274
- References
- 39
- Citations by year
- 2026: 27 · 2025: 35 · 2024: 29 · 2023: 45 · 2022: 40 · 2021: 48 · 2020: 39 · 2019: 10
- FWCI
- 22.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion, other-oa)
- Funders
- University of Southern Denmark
- 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, celiac serology, anti-tissue transglutaminase IgA, anti-endomysial antibodies, duodenal biopsy, Marsh classification, IgA deficiency, gluten-free diet, disease surveillance, children and adolescents, differential diagnosis, morphometrics, positive predictive value, upper gastrointestinal endoscopy
- MeSH terms
- Protein Glutamine gamma Glutamyltransferase 2, Algorithms, Biopsy, Celiac Disease, Duodenum, Gliadin, Humans, Immunoglobulin A, Immunoglobulin G, Population Surveillance, Transglutaminases, Serologic Tests, GTP-Binding Proteins
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