title: In vitro gliadin challenge: diagnostic accuracy and utility for the difficult diagnosis of celiac disease.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Tortora
authors.forename: Ilaria
authors.initials: I
authors.lastname: Russo
authors.forename: Giovanni D
authors.initials: GD
authors.lastname: De Palma
authors.forename: Alessandro
authors.initials: A
authors.lastname: Luciani
authors.forename: Antonio
authors.initials: A
authors.lastname: Rispo
authors.forename: Fabiana
authors.initials: F
authors.lastname: Zingone
authors.forename: Paola
authors.initials: P
authors.lastname: Iovino
authors.forename: Pietro
authors.initials: P
authors.lastname: Capone
authors.forename: Carolina
authors.initials: C
authors.lastname: Ciacci
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis; D002446:Celiac Disease / Q000175:diagnosis* / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005903:Gliadin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; D005903:Gliadin