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Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis.

ABSTRACT: The need of adding the determination of anti-deamidated gliadin peptide (DGP) IgG to anti-transglutaminase (TTG) IgA antibodies for diagnosis of celiac disease (CD) in children <2 years of age is controversial. We performed a systematic review and meta-analysis to evaluate, by head-to-head comparison, the diagnostic accuracy of TTG IgA and DGP IgG antibodies. We searched PubMed, MEDLINE, and Embase databases up to January 2021. The diagnostic reference was intestinal biopsy. We calculated the sensitivity and specificity of these tests and the odds ratio (OR) between the tests. Fifteen articles were eligible for the systematic review and ten were eligible for the meta-analysis. Sensitivity and specificity were 0.96 (95% confidence interval (CI), 0.91-0.98) and 0.96 (95% CI, 0.85-0.99) for DGP IgG and 0.93 (95% CI, 0.88-0.97) and 0.98 (95% CI, 0.96-0.99) for TTG IgA, respectively. TTG IgA specificity was significantly higher (OR 9.3 (95% CI, 2.3-37.49); p < 0.001) while the sensitivity of DGP IgG was higher without reaching statistical significance (OR: 0.6 (95% CI, 0.24-1.51); p = 0.28). Both the meta-analysis and the systematic review showed that some children with early CD are missed without the DGP IgG test. In children <2 years of age, TTG IgA is the best CD screening test; however, the addition of DGP IgG may increase the diagnostic sensitivity.

SUBMITTER: Catassi GN

PROVIDER: S-EPMC8746847 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundInternational guidelines recommend coeliac serology in iron deficiency anaemia, and duodenal biopsy for those tested positive to detect coeliac disease. However, pre-endoscopy serology is often unavailable, thus committing endoscopists to take routine duodenal biopsies. Some endoscopists consider duodenal biopsy mandatory in anaemia to exclude other pathologies. We hypothesise that using a point of care test at endoscopy could fill this gap, by providing rapid results to target anaemic patients who require biopsies, and save costs by biopsy avoidance. We therefore assessed three key aspects to this hypothesis: 1) the availability of pre-endoscopy serology in anaemia; 2) the sensitivities and cost effectiveness of pre-endoscopy coeliac screening with Simtomax in anaemia; 3) whether other anaemia-related pathologies could be missed by this targeted-biopsy approach.MethodsGroup 1: pre-endoscopy serology availability was retrospectively analysed in a multicentre cohort of 934 anaemic patients at 4 UK hospitals. Group 2: the sensitivities of Simtomax, endomysial and tissue-transglutaminase antibodies were compared in 133 prospectively recruited patients with iron deficiency anaemia attending for a gastroscopy. The sensitivities were measured against duodenal histology as the reference standard in all patients. The cost effectiveness of Simtomax was calculated based on the number of biopsies that could have been avoided compared to an all-biopsy approach. Group 3: the duodenal histology of 153 patients presenting to a separate iron deficiency anaemia clinic were retrospectively reviewed.ResultsIn group 1, serology was available in 361 (33.8 %) patients. In group 2, the sensitivity and negative predictive value (NPV) were 100 % and 100 % for Simtomax, 96.2 % and 98.9 % for IgA-TTG, and 84.6 % and 96.4 % for EMA respectively. In group 3, the duodenal histology found no causes for anaemia other than coeliac disease.ConclusionSimtomax had excellent diagnostic accuracy in iron deficiency anaemia and was comparable to conventional serology. Duodenal biopsy did not identify any causes other than coeliac disease for iron deficiency anaemia, suggesting that biopsy avoidance in Simtomax negative anaemic patients is unlikely to miss other anaemia-related pathologies. Due to its 100 % NPV, Simtomax could reduce unnecessary biopsies by 66 % if only those with a positive Simtomax were biopsied, potentially saving £3690/100 gastroscopies.Trial registrationThe group 2 study was retrospectively registered with clinicaltrials.gov. Trial registration date: 13(th) July 2016;Trial registration numberNCT02834429 .

Project description:BackgroundCeliac serology has evolved, with the identification of newer antibodies against deamidated gliadin peptides (DGP) [e.g., anti-DGP, immunoglobulin A (IgA), and immunoglobulin G (IgG) types] with sensitivity and specificity in detecting celiac disease (CeD) that are equivalent to anti-tissue transglutaminase [anti-tissue transglutaminase (TTG) IgA]-based tests, particularly in populations with high pretest probability of CeD (prevalence of CeD > 50% of the population under study). This opens the possibility that anti-DGP assays can be used to identify CeD in the general population where the prevalence of CeD is very low (≈1%).ObjectiveThis study aimed (1) to determine the diagnostic performance of DGP antibodies-based serologic assays in identifying CeD during the screening of the general population and (2) to compare the levels of anti-DGP antibodies among CeD patients with mild and severe degrees of enteropathy.MethodsSerology tests for DGP antibodies (DGP-IgA, DGP-IgG, and conjugate TTG/DGP antibodies) were performed on 104 serum samples of positive TTG-IgA (100 confirmed and four potential celiac patients) and a randomly selected 1,000 negative TTG-IgA serum samples collected during mass screening of children (aged 6-15 years) in 2014-2015.ResultsSera from 32 of the 1,000 TTG-IgA negative serum specimens (3.2%) tested positive for one or more of the three anti-DGP serology tests. A total of 13 of the 32 anti-DGP seropositive patients had persistent positive results on follow-up samples in 2020 (1.3%). Eight of the 13 underwent endoscopy with biopsies, and only two had confirmed CeD (both DGP-IgG positive) (0.2%). The sensitivity and specificity of the serology assays were as follows: DGP-IgA (62.7%, 40%), DGP-IgG (80.4%, 100%), and conjugate TTG/DGP (96%, 10%). Based on receiver operating characteristic curves, the area under the curve for DGP-IgG (0.919; 95% CI -0.00406 to 0.114) was comparable to TTG-IgA (0.974; 95% CI 0.924-0.995) (P = 0.0679). Titers of antibodies to DGPs were significantly higher in children with severe intestinal damage than in those in children with mild lesions (P < 0.001).ConclusionThe TTG-IgA assay remains the most reliable screening serology test for CeD in mass screening studies. The performance of TTG-IgA has improved marginally by adding DGP-IgG to the mass screening protocol. In CeD patients detected by mass screening, the anti-DGP antibody titer was significantly higher among patients with a severe degree of enteropathy as compared to the group with mild enteropathy.

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Diagnostic Accuracy of IgA Anti-Transglutaminase and IgG Anti-Deamidated Gliadin for Diagnosis of Celiac Disease in Children under Two Years of Age: A Systematic Review and Meta-Analysis.

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