From the Guidelines
A negative Endomysial Antibody (IgA) test and a t-Transglutaminase (tTG) IgA level less than 2 U/mL strongly suggest that celiac disease is unlikely. These results are considered normal and do not support a diagnosis of celiac disease. If the patient has been consuming gluten regularly before testing, these negative results are particularly reliable, as noted in the guidelines for the diagnosis and management of adult coeliac disease 1. However, it's essential to consider that if the patient has been on a gluten-free diet prior to testing, these negative results could be misleading since antibody levels decrease when gluten is removed from the diet, as advised by the AGA clinical practice update on diagnosis and monitoring of celiac disease 1. Additionally, these results assume normal total IgA levels; if a patient has IgA deficiency, which affects about 2-3% of celiac patients, false negative results can occur, highlighting the importance of obtaining or reviewing serum total IgA levels in patients with possible seronegative CeD, as recommended in the AGA clinical practice update on the evaluation and management of seronegative enteropathies 1. In cases where symptoms strongly suggest celiac disease despite negative antibody tests, additional testing such as genetic testing for HLA-DQ2/DQ8 or an intestinal biopsy might be warranted, following the algorithm for the diagnosis of coeliac disease provided by the British Society of Gastroenterology 1. The high specificity of tTG IgA (95-99%) and EMA IgA (nearly 100%) makes these negative results particularly reassuring in ruling out celiac disease in most clinical scenarios.
Some key points to consider in the interpretation of these results include:
- The patient's dietary history, particularly gluten consumption, before testing
- The presence of IgA deficiency, which can lead to false negative results
- The high specificity of tTG IgA and EMA IgA in ruling out celiac disease
- The potential need for additional testing in cases with strong clinical suspicion despite negative antibody tests
Given the most recent and highest quality evidence, the combination of a negative Endomysial Antibody (IgA) and a t-Transglutaminase (tTG) IgA level less than 2 U/mL is highly suggestive that celiac disease is not present, assuming normal total IgA levels and recent gluten consumption, as supported by the guidelines and updates from reputable sources 1.
From the Research
Interpretation of Celiac Disease Panel Results
- A negative Endomysial Antibody (IgA) result indicates a low likelihood of celiac disease, as endomysial IgA antibodies have over 99% specificity for gluten-sensitive enteropathy 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.
- The combination of a negative Endomysial Antibody (IgA) and a negative t-Transglutaminase (tTG) IgA result suggests that celiac disease is unlikely, but it is essential to consider the clinical context and other diagnostic criteria.
Diagnostic Considerations
- The sensitivity and specificity of tTG IgA and EMA IgA assays in identifying patients with celiac disease who have persistent villous atrophy despite a gluten-free diet have been evaluated in several studies 3, 4.
- These studies suggest that while the assays have high specificity, their sensitivity is lower, and they may not detect all cases of celiac disease, particularly in patients with persistent villous atrophy on a gluten-free diet.
- The use of multiple assays and consideration of clinical context are recommended to improve diagnostic accuracy 5, 6.
Clinical Implications
- A negative Celiac Disease Panel result does not entirely rule out celiac disease, and further evaluation may be necessary in patients with persistent symptoms or clinical suspicion of celiac disease.
- The choice of assay and interpretation of results should be considered in the context of clinical presentation, medical history, and other diagnostic findings 6.