To report the evidence on comparative accuracy and safety of methods used in current clinical practice to diagnose celiac disease, including serological tests, human leukocyte antigen (HLA) typing, and video capsule endoscopy. Diagnostic tests used singly and in combination in various populations were compared against the reference standard of endoscopic duodenal biopsy. In addition, factors affecting biopsy accuracy were reviewed.

Data Sources

Electronic searches of PubMed [registered trademark], Embase [registered trademark], the Cochrane Library, and Web of Science from 1990 through March 2015. Reference lists of included publications were searched for additional relevant studies, and experts were asked to suggest studies.

Review Methods

Studies of diagnostic accuracy were included if all participants underwent the index test and endoscopy with duodenal biopsy as the reference standard. Systematic reviews on accuracy and studies on adverse events associated with testing were included. Standard assessment tools were used to evaluate study risk of bias. Where possible, results of accuracy studies were pooled using meta-analysis. When pooling was not possible, findings were described narratively and presented in tables and figures.


A total of 7,254 titles were identified, from which 60 individual studies and 13 prior systematic reviews were included. The majority of studies were conducted in participants with symptoms. New meta-analyses found high-strength evidence to support excellent accuracy of anti-tissue transglutaminase (tTG) immunoglobulin A (IgA) tests (sensitivity = 92.5%; specificity = 97.9%) and excellent specificity of endomysial antibodies (EmA) IgA tests (sensitivity = 79.0%; specificity = 99.0%), as reported in previous systematic reviews. Promising results were reported for deamidated gliadin peptide antibodies (DGP) IgA tests (sensitivity = 87.8%; specificity = 94.1%) in a recent meta-analysis. Evidence for algorithms using multiple tests was insufficient because of diverse results, low number of studies, and heterogeneity of populations. Evidence was also insufficient for accuracy in asymptomatic general population screening and special populations such as children and patients with type 1 diabetes, anemia, and IgA deficiency.


New evidence on accuracy of tests used to diagnose celiac disease supports the excellent sensitivity of tTG IgA tests and excellent specificity of both tTG IgA and EmA IgA tests. Sensitivity of DGP IgA and immunoglobulin G tests is slightly less than for tTG IgA. Additional studies are needed to confirm the accuracy of diagnostic tests in special populations and to validate promising algorithms.

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