Systematic Review and Meta-Analysis of the Sensitivity and Specificity of TTG and EMA IgA antibodies for persistent mucosal damage in persons with celiac disease following a gluten-free diet: Literature search documentation

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Szwajcer, Andrea
Silvester, Jocelyn
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Background: Serum anti-endomysial (EMA) and anti-tissue transglutaminase (tTG) antibody tests were initially developed to screen for celiac disease in patients consuming gluten; however, they are commonly used to monitor patients with celiac disease on a gluten-free diet. Aims: To determine the utility (sensitivity and specificity) of tTG IgA and EMA IgA for detecting persistent mucosal damage in patients with biopsy confirmed celiac disease on a gluten free diet (GFD). Methods: We systematically searched PUBMED, EMBASE, BIOSIS, SCOPUS,, Science Citation Index, and the Cochrane Library without language restriction through January 2016. Inclusion criteria for eligible studies were (1) subjects with a biopsy confirmed diagnosis of celiac disease; (2) follow-up endoscopy on a gluten-free diet; (3) serum antibody measurement contemporaneous with biopsy (as defined by the authors); (4) biopsy of subjects with both negative and positive antibody testing; (5) sufficient data presented to enable construction of contingency tables. Subjects with refractory celiac disease, undergoing gluten challenge, or consuming a prescribed oats-containing gluten-free diet were excluded. For biopsy specimens, Marsh 0 and 1 were considered negative and Marsh 2 and 3a-c were considered positive. Antibody testing was documented as positive or negative using the cut-offs reported by the authors. Results: Initial search identified 3792 unique citations. Abstracts were reviewed and 285 were selected for detailed review of the entire article. Only 22 studies of tTG and 53 studies of EMA met criteria for inclusion in the analysis. The most common reason for exclusion was inability to link individual results to produce a 2x2 table from the data as presented. For tTG, sensitivity varied from 0% to 80% and specificity varied from 50% to 100%. For EMA, sensitivity varied from 0% to 100% and specificity varied from 67% to 100%. SROC curves depict an area under the curve (AUC) of 0.68 for tTG and 0.80 for EMA. Conclusions: Serum levels of tTG IgA and EMA IgA are insensitive for persistent mucosal damage once patients have adopted a gluten-free diet. The variable sensitivity leads to false negative tests more frequently for tTG than for EMA. More accurate non-invasive markers of mucosal damage in persons with celiac disease who are following a gluten-free diet are required.
This report is the literature search documentation that supports the systematic review and meta-analysis research.
systematic review, sensitivity and specificity, TTG, EMA IgA, Celiac disease, literature search, gluten-free diet