For those in our patient community interested in doing a deeper dive on the topic of celiac disease diagnosis, we are happy to provide here expert commentary from Dr. Robert Anderson, MB ChB PhD. 

A strongly elevated transglutaminase IgA blood test result accurately predicts celiac disease in high-risk patients according to a report in the September edition of Lancet Gastroenterology & Hepatology. The authors conclude that a serology-based celiac disease diagnosis without biopsy is possible in adults with strong suspicion of coeliac disease (high pretest probability) – 81% of the 436 patients consecutively enrolled in this prospective observational study had biopsy-confirmed celiac disease. The researchers led by Professor Carolina Ciacci found that only one in 30 adults with a transglutaminase IgA level five or more-times higher than the upper level of normal did not have celiac disease confirmed by duodenal biopsy. Even at lower but still elevated transglutaminase IgA levels only one in eight patients did not have celiac disease. On the other hand, the transglutaminase IgA blood test overlooked celiac disease in 10% of patients who presented with symptoms associated with a high likelihood of celiac disease.  

The United States FDA approves transglutaminase IgA tests such as the one employed by the central laboratory in the Ciacci study as an “aid” in the diagnosis of celiac disease and dermatitis herpetiformis “in conjunction with clinical findings and other laboratory tests.” Although Ciacci and colleagues as well as authors of several other similar but retrospective studies have argued the performance and operational benefits of serology-only diagnosis, these come at a cost to patients. Avoiding biopsy is attractive for healthcare systems with insufficient endoscopy services and in patients who cannot access specialist services due to cost or supply. Misdiagnoses due to false positive transglutaminase IgA were unusual in this study, but false negative serology was rather common in patients strongly suspected of having celiac disease. In some healthcare systems, these may be acceptable “mistakes” but ultimately the downside is for patients who receive inaccurate diagnoses. Gastroenterologists are currently the physician group trained to be specialists in adult celiac disease. There remains a worry that serology-based endoscopy-free diagnosis may inadvertently exclude the gastroenterologist from the management of patients with celiac disease.  

Serology is a powerful tool when addressing the possibility of celiac disease. European experts have advocated for a tiered approach to diagnosis with repeated very high transglutaminase IgA levels being sufficient for diagnosis in adults and children, but in other patients with lower or normal levels of transglutaminase IgA additional tests appear to be necessary to rule in or rule out celiac disease. 

Disclosure: Robert Anderson is President of the International Society for the Study of Celiac Disease and is Director and shareholder in Novoviah Pharmaceuticals Ltd – a company developing blood-based tests for celiac disease, and also advises industry in the development of therapeutics for celiac disease. He is the recipient of the 2023 Celiac Disease Foundation Prize for Excellence in Celiac Disease Research.