Bye Bye Biopsy for Adults with Celiac Serology 10 Times Higher Than Normal

bye bye biopsy celiac disease wpA recent study by a team of researchers confirmed that most adults do not require a biopsy for a reliable celiac disease diagnosis.

  • BMJ Journals, 1

Significance of this study

What is already known on this subject?

  • European Society for the Study of Paediatric Gastroenterology, Hepatology and Nutrition guidelines suggest that a diagnosis of coeliac disease (CD) can be made without taking duodenal biopsies.
  • The latest criteria suggest that a 10-fold increase in IgA antitissue transglutaminase (tTG) antibody levels in combination with EMA positivity is sufficient to make a diagnosis of CD in the absence of duodenal biopsies.
  • In adults, this approach has not yet been widely adopted into clinical practice, largely due to a lack of international multicentre data and testing in low CD prevalence cohorts.

What are the new findings?

  • Across three cohorts of adult patients, we have shown that almost all individuals with IgA tTG titres of ≥10×ULN have small intestinal mucosal changes diagnostic of CD (Marsh 3 lesions) on duodenal biopsy.
  • We show that IgA tTG titres of 10×ULN have 100% specificity at detecting Marsh 3 lesions in a cohort of 532 adults with a CD prevalence of 3.2%.
  • Finally, we found that an IgA tTG cut-off of 10×ULN performed well at identifying individuals with Marsh 3 lesions using different assays across multiple international sites. However, determining assay-specific thresholds and/or standardisation of tTG assays used with this pathway may help to optimise the accuracy and impact of this approach.

How might it impact on clinical practice in the foreseeable future?

  • This study supports a change in guidelines towards a no-biopsy approach for the diagnosis of CD within adult gastroenterology services.

The Study


We aimed to determine the predictive capacity and diagnostic yield of a 10-fold increase in serum IgA anti-tissue trans-glutaminase (tTG) antibody levels for detecting small intestinal injury diagnostic of coeliac disease (CD) in adult patients.


The study comprised three adult cohorts.

  • Cohort 1: 740 patients assessed in the specialist CD clinic at a UK centre;
  • cohort 2: 532 patients with low suspicion for CD referred for upper GI endoscopy at a UK centre;
  • cohort 3: 145 patients with raised tTG titres from multiple international sites.

Marsh 3 histology was used as a reference standard against which we determined the performance characteristics of an IgA tTG titre of ≥10×ULN for a diagnosis of CD.


  • Cohort 1: the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 54.0%, 90.0%, 98.7% and 12.5%, respectively.
  • Cohort 2: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 50.0%, 100.0%, 100.0% and 98.3%, respectively.
  • Cohort 3: the sensitivity, specificity, PPV and NPV for IgA tTG levels of ≥10×ULN at identifying individuals with Marsh 3 lesions were 30.0%, 83.0%, 95.2% and 9.5%, respectively.


Our results show that IgA tTG titres of ≥10×ULN have a strong predictive value at identifying adults with intestinal changes diagnostic of CD. This study supports the use of a no-biopsy approach for the diagnosis of adult CD.

Read the entire article here. 

Authors: Hugo A Penny1, Suneil A Raju, Michelle S Lau, Lauren JS Marks, Elisabeth MR Baggus1, Julio C Bai, Gabrio Bassotti, Hetty J Bontkes, Antonio Carroccio, Mihai Danciu, Mohammad H Derakhshan, Arzu Ensari, Azita Ganji, Peter H R Green, Matt W Johnson, Sauid Ishaq, Benjamin Lebwohl, Adam Levene, Roxana Maxim, Hamid Mohaghegh Shalmani, Mohammad Rostami-Nejad, David Rowlands, Irene A Spiridon, Amitabh Srivastava, Umberto Volta, Vincenzo Villanacci, Graeme Wild, Simon S Cross, Kamran Rostami, David S Sanders.