Colon/Small Bowel

Subject Category: Colon/Small Bowel

Am J Gastroenterol 2012; 107:111–117; doi:10.1038/ajg.2011.311; published online 27 September 2011

In Vitro Gliadin Challenge: Diagnostic Accuracy and Utility for the Difficult Diagnosis of Celiac Disease

Raffaella Tortora MD1, Ilaria Russo PhD1, Giovanni D De Palma MD2, Alessandro Luciani PhD3, Antonio Rispo MD1, Fabiana Zingone MD1, Paola Iovino MD4, Pietro Capone MD1 and Carolina Ciacci MD4

  1. 1Department of Clinical and Experimental Medicine, Federico II University of Naples, Naples, Italy
  2. 2Department of Surgery, Endoscopy Unit, Federico II University of Naples, Naples, Italy
  3. 3Institute of Pediatrics, University of Foggia, Foggia, Italy
  4. 4University of Salerno, School of Medicine, Gastroenterology, Campus di Baronissi, Salerno, Italy

Correspondence: Carolina Ciacci, MD, University of Salerno, School of Medicine, Gastroenterology, Campus di Baronissi, via S. Allende 84081 Baronissi (SA), Salerno 80131, Italy. E-mail: or

Received 8 November 2010; Accepted 14 August 2011; Published online 27 September 2011.





Diagnosis of celiac disease is difficult when treatment with gluten-free diet (GFD) is started before diagnosis and/or when the results of tests are inconsistent. The objective of this study was to evaluate the in vitro gliadin challenge.



The study cohort included patients without celiac disease (negative controls, n=57), patients with celiac disease (positive controls, n=166 untreated and n=55 on GFD), and patients with difficult diagnosis (n=59). All patients underwent endoscopy for collection of duodenal samples, which served for the diagnosis of celiac disease and for the in vitro evaluation of the gliadin-induced mucosal expression of seven inflammatory markers: PY99, ICAM-1 (intercellular cell adhesion molecule), HLA-DR, CD3, CD25, CD69, and transglutaminase 2 IgA. Diagnostic work-up for celiac disease included the search of specific serum antibodies. Patients of the difficult diagnosis group were asked to stop GFD for repeated search of these antibodies under untreated conditions. The area under the receptor-operated curve (ROC) was used for statistical analyses on accuracy.



HLA-DR had the highest accuracy for celiac disease diagnosis in analyses on negative controls and positive controls also excluding patients on GFD (area under ROC=0.99). Accuracy of test did not increase combining data of HLA-DR with data of other markers. Findings were similar in the 39 patients of the difficult diagnosis group undergoing the search celiac disease-specific antibodies under untreated conditions.



The in vitro response of mucosal HLA-DR to gliadin is an accurate tool for the diagnosis of celiac disease also in patients with difficult diagnosis.