From the Guidelines
The positive predictive value (PPV) of anti-Tissue Transglutaminase (TTG) for celiac disease is approximately 80-90% in individuals with high titers (>10 times the upper limit of normal) 1.
Key Points
- In patients with symptoms suggestive of celiac disease, a positive anti-TTG result is highly suggestive of the condition, with a PPV of 95% or higher 1.
- A cutoff value of 10 times the upper limit of normal for anti-TTG IgA is commonly used to define a positive result, although this may vary depending on the specific assay used 1.
- The British Society of Paediatric Gastroenterology, Hepatology and Nutrition guidelines have incorporated the safe and secure serological diagnosis of coeliac disease, allowing children meeting certain criteria to be diagnosed without biopsy 1.
- There is increasing evidence of the high predictive value of IgA tTG ≥10× the upper limit of normal in an adult population, with interim guidance including a non-biopsy protocol for adults with suspected coeliac disease published in light of the coronavirus pandemic 1.
Important Considerations
- The interpretation of serological test results remains an important area of research, and further work is needed to confirm the thresholds above and below which we can confidently rule in or rule out coeliac disease 1.
- The practice of dichotomising continuous test results may be an oversimplification of a complex disease with a wide range of clinical presentations 1.
- Further research is also needed to estimate the accuracy of serological tests used in sequence or combination and to model the clinical and cost effectiveness of tests and testing strategies 1.
From the Research
Positive Predictive Value of Anti-Tissue Transglutaminase for Celiac Disease
- The positive predictive value of IgA anti-tissue transglutaminase for celiac disease has been reported in several studies:
- A study published in 1999 found a positive predictive value of 92% 2
- A study published in 2004 found a positive predictive value of 54% for IgA anti-tissue transglutaminase, but 97% for dual positivity for anti-tissue transglutaminase and anti-endomysium antibody 3
- A study published in 2021 found a positive predictive value of 94.2% for an anti-tissue transglutaminase antibody titer greater than 84.6 U/ml 4
- A study published in 2012 found a positive predictive value of 100% for an anti-tissue transglutaminase ratio ≥ 7, confirmed by positivity to anti-endomysium antibody 5
- A study published in 2006 found a positive predictive value of 91.1% for the anti-tissue transglutaminase antibody test, but noted significant variability in test characteristics among commercial laboratories 6
Variability in Positive Predictive Value
- The positive predictive value of anti-tissue transglutaminase for celiac disease can vary depending on the study population, laboratory, and assay used:
- The study published in 2006 found significant differences in sensitivity and specificity between two commercial laboratories 6
- The study published in 2012 found that an anti-tissue transglutaminase ratio ≥ 7 was able to identify all patients with significant mucosal damage, independent of age and sex 5
- The study published in 2021 found that an anti-tissue transglutaminase antibody titer greater than 84.6 U/ml was significantly associated with Marsh grade greater than two 4
Clinical Utility of Anti-Tissue Transglutaminase
- The clinical utility of anti-tissue transglutaminase for the diagnosis of celiac disease is supported by several studies:
- The study published in 2004 found that IgA anti-tissue transglutaminase was a useful initial screen for celiac disease, but that positive results should be confirmed with the more accurate anti-endomysium antibody assay 3
- The study published in 2012 found that patients with positivity of anti-tissue transglutaminase ≥ 7-fold cutoff, confirmed by positivity to anti-endomysium antibody, have a high-degree probability of duodenal damage 5