Serum anti-tissue transglutaminase IgA aids better diagnosis of Coeliac Disease in Adults: Lancet

In a recent study published in The Lancet Gastroenterology & Hepatology compelling evidence that the serum anti-tissue transglutaminase IgA (tTG-IgA) test, can accurately diagnose coeliac disease in adults. Coeliac disease, an autoimmune disorder triggered by the ingestion of gluten, has traditionally required invasive diagnostic procedures such as endoscopic duodenal biopsy to confirm the presence of duodenal villous atrophy. However, whether serology alone can reliably diagnose coeliac disease in adults has been a matter of debate within the medical community.

To address this controversy, a multicentre prospective cohort study was conducted involving 14 tertiary referral centres across Europe, Asia, Oceania, and South America. The study, which ran from February 27, 2018, to December 24, 2020, enrolled adult participants aged 18 and above with suspected coeliac disease, who were not on a gluten-free diet and did not have IgA deficiency. These participants underwent local endoscopic duodenal biopsy after a local serum tTG-IgA measurement, using 14 different test brands.

Of the 436 participants with complete data, 363 (83%) tested positive for serum tTG-IgA, while 73 (17%) tested negative. Of those with positive serum tTG-IgA, 341 had positive duodenal histology (true positives), and 22 had negative histology (false positives) based on local review. In contrast, among the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives), and 66 had negative histology (true negatives).

The study found that the positive predictive value of serum tTG-IgA was 95.9% and the negative predictive value was 90.4% after central re-evaluation of duodenal histology in discordant cases. The sensitivity was 98.0%, and specificity was 81.5%. The area under the receiver operating characteristic curve (AUC) for serum tTG-IgA was 0.93, indicating its high diagnostic accuracy.

These findings suggest that for adults with reliable suspicion of coeliac disease and high serum tTG-IgA, a biopsy may be reasonably avoided. This could significantly reduce the need for invasive procedures, leading to quicker diagnosis and treatment initiation for coeliac disease.

The study also reported various endoscopic findings, including peptic gastritis, autoimmune atrophic gastritis, reflux oesophagitis, and more. Notably, a case of midgut ileum lymphoma was diagnosed in a woman on a gluten-free diet during the 1-year follow-up, highlighting the importance of accurate diagnosis and monitoring in coeliac disease patients. 

Reference:

Ciacci, C., Bai, J. C., Holmes, G., Al-Toma, A., Biagi, F., Carroccio, A., Ciccocioppo, R., Di Sabatino, A., Gingold-Belfer, R., Jinga, M., Makharia, G., Niveloni, S., Vivas, S., & Zingone, F. (2023). Serum anti-tissue transglutaminase IgA and prediction of duodenal villous atrophy in adults with suspected coeliac disease without IgA deficiency (Bi.A.CeD): a multicentre, prospective cohort study. In The Lancet Gastroenterology & Hepatology. Elsevier BV. https://doi.org/10.1016/s2468-1253(23)00205-4