From the Guidelines
A negative Endomysial Antibody (IgA) test and a t-Transglutaminase (tTG) IgA level of less than 2 U/mL in a Celiac Disease Panel strongly suggests that celiac disease is unlikely. These results are considered normal and do not support a diagnosis of celiac disease, as supported by the guidelines for best practices in monitoring established coeliac disease in adult patients 1. If the patient has been consuming gluten regularly before testing, these negative results are particularly reliable. However, it's essential to note that if the patient has been on a gluten-free diet prior to testing, false negative results can occur, as highlighted in the systematic review with meta-analysis on the accuracy of serological tests for diagnosing coeliac disease 1. Additionally, these results should be interpreted in the context of total IgA levels, as IgA deficiency (present in about 2-3% of celiac patients) can lead to false negative antibody tests, as discussed in the AGA clinical practice update on the evaluation and management of seronegative enteropathies 1. Some key points to consider in the interpretation of these results include:
- The importance of consuming a gluten-containing diet before testing to ensure accurate results, as emphasized in the AGA clinical practice update on diagnosis and monitoring of celiac disease 1.
- The need to measure total IgA levels to rule out IgA deficiency, which can lead to false negative results, as noted in the guidelines from the British Society of Gastroenterology 1.
- The potential for false negative results in patients with IgA deficiency, and the need for IgG-based testing in such cases, as discussed in the AGA clinical practice update on the evaluation and management of seronegative enteropathies 1. If celiac disease is still strongly suspected despite these negative results, additional testing such as genetic testing for HLA-DQ2 and HLA-DQ8 or an intestinal biopsy might be warranted. Patients with negative celiac markers who have been consuming gluten can generally continue a normal diet containing gluten unless other clinical indications suggest otherwise. It is crucial to consider the patient's clinical presentation, medical history, and other diagnostic findings when interpreting these results, as emphasized in the guidelines for best practices in monitoring established coeliac disease in adult patients 1.
From the Research
Interpretation of Celiac Disease Panel Results
- A negative Endomysial Antibody (IgA) result indicates that the patient does not have antibodies against endomysial tissue, which are typically present in individuals with celiac disease 2.
- A t-Transglutaminase (tTG) IgA level of less than 2 U/mL is considered negative, as the normal range is 0-3 U/mL, and levels above 10 U/mL are typically considered positive 3.
Considerations for IgA Deficiency
- IgA deficiency can cause false-negative results for IgA-based celiac serology tests, including Endomysial Antibody (IgA) and t-Transglutaminase (tTG) IgA tests 3.
- In patients with IgA deficiency, alternative tests such as IgG-tissue transglutaminase or intestinal biopsy may be necessary to diagnose celiac disease 3.
Clinical Implications
- A negative Endomysial Antibody (IgA) result and a t-Transglutaminase (tTG) IgA level of less than 2 U/mL suggest that the patient is unlikely to have celiac disease, but do not completely rule out the possibility 4, 5.
- Patients with clinical symptoms suggestive of celiac disease and negative serology results may require further evaluation, including intestinal biopsy or other diagnostic tests 5, 6.
Limitations of Serological Tests
- Serological tests for celiac disease, including Endomysial Antibody (IgA) and t-Transglutaminase (tTG) IgA tests, have limitations in terms of sensitivity and specificity, and may not detect all cases of celiac disease 2, 6.
- The use of multiple serological tests and clinical evaluation is recommended to improve the accuracy of celiac disease diagnosis 4, 5.