From the Guidelines
To determine gluten-free status in celiac disease (CD), the most reliable diagnostic tests are serology, specifically tissue transglutaminase antibodies (TG2Ab) with high sensitivity (93%) and specificity (98%), followed by duodenal biopsy if serology is positive, as recommended by the most recent guidelines 1.
Diagnostic Approach
The diagnostic approach for CD involves:
- Serology testing for TG2Ab as the first-line screening test
- Serum analysis of anti-endomysial antibodies (EMAs) as a second-line test with high specificity
- HLA typing in uncertain cases, as nearly 100% of individuals with CD exhibit HLA-DQ2 and/or HLA-DQ8 molecules
- Duodenal biopsy to evaluate small bowel damage, with histological assessment of villous to crypt cell ratio and Marsh and Marsh-Oberhuber score systems
Importance of Gluten Consumption Before Testing
It is crucial to continue eating gluten before testing for CD, as eliminating gluten beforehand can lead to false-negative results. For accurate results, a person should consume the equivalent of at least four slices of bread daily for 6-8 weeks before testing.
Recent Guidelines and Recommendations
Recent guidelines from the British Society of Gastroenterology 1 and a systematic review with meta-analysis 1 support the use of serological tests and duodenal biopsy for CD diagnosis. Additionally, an expert review on the evaluation and management of seronegative enteropathies provides best practice advice on CD diagnosis and management 1.
Key Points
- Serology testing, specifically TG2Ab, is the first-line screening test for CD
- Duodenal biopsy is necessary to evaluate small bowel damage and confirm CD diagnosis
- HLA typing can help rule out CD in uncertain cases
- Continued gluten consumption before testing is essential for accurate results
From the Research
Diagnostic Tests for Celiac Disease
The diagnostic tests for celiac disease (CD) to determine gluten-free status include:
- Immunoglobulin A tissue transglutaminase serologic testing, which is the recommended initial screening for all age groups 2
- Esophagogastroduodenoscopy with small bowel biopsy, which is recommended to confirm the diagnosis in most patients, including those with a negative serologic test for whom clinical suspicion of celiac disease persists 2
- Genetic testing for human leukocyte antigen alleles DQ2 or DQ8, which may be performed in select cases 2
- Tests for serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG), which can be used to monitor patients on a gluten-free diet (GFD) 3
- Antigliadin tests, which are no longer recommended for the diagnosis of classical celiac disease, but may be useful in the diagnosis of gluten-sensitive irritable bowel syndrome 4
Sensitivity and Specificity of Diagnostic Tests
The sensitivity and specificity of diagnostic tests for celiac disease vary:
- Immunoglobulin A tissue transglutaminase serologic testing has a high sensitivity and specificity 2, 5
- Tests for serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) have high specificity, but low sensitivity in detecting persistent villous atrophy in patients on a GFD 3
- Different tissue transglutaminase IgA assays have different characteristics for monitoring response to GFD, with some assays being more sensitive than others 6
Monitoring Patients on a Gluten-Free Diet
Monitoring patients with celiac disease on a gluten-free diet is important:
- Serum tests, such as tissue transglutaminase IgA and endomysial antibodies, can be used to monitor diet compliance 2, 3, 6
- Intestinal fatty acid binding protein (i-FABP) can be used as a surrogate marker for intestinal epithelial damage in patients on a GFD 6
- Small intestinal biopsy is still recommended as a "gold standard" for diagnosis and monitoring of celiac disease, especially in cases where serum tests are negative or inconclusive 2, 5