title: Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity.
abstract: OBJECTIVE
  Nonceliac gluten-sensitive (NCGS) patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten; these symptoms disappear on gluten-free diets, although these patients have no serologic markers of celiac disease or intestinal damage. In fact, there is no evidence for mucosal or serologic modifications in those individuals. We investigated immunologic responses of duodenal mucosa samples and peripheral blood basophils, isolated from NCGS patients, after exposure to gliadin.
  
  
  METHODS
  Participants underwent a complete clinical evaluation to exclude celiac disease while on a gluten-containing diet, a skin prick test to exclude wheat allergy, and upper endoscopy (n = 119) at 2 tertiary medical centers in Italy. Patients were considered to have NCGS based on their symptoms and the current definition of the disorder. Subjects were assigned to the following groups: patients with celiac disease on gluten-free diets (n = 34), untreated patients with celiac disease (n = 35), patients with NCGS (n = 16), or controls (n = 34). Duodenal biopsy samples collected during endoscopy were incubated with gliadin peptides, and levels of inflammatory markers were assessed. Peripheral blood basophils were extracted and incubated with gliadin peptides or a mix of wheat proteins; activation was assessed based on levels of CD203c, CD63, and CD45.
  
  
  RESULTS
  Duodenal mucosa samples collected from 69 patients with celiac disease showed markers of inflammation after incubation with gliadin. Some, but not all, markers of inflammation were detected weakly in biopsy samples from 3 controls and 3 NCGS patients (P = .00 for all markers). There were no significant increases in the levels of CD63 and CD203c in NCGS patients.
  
  
  CONCLUSIONS
  Unlike the duodenal mucosa from patients with celiac disease, upon incubation with gliadin, mucosa from patients with NCGS does not express markers of inflammation, and their basophils are not activated by gliadin. The in vitro gliadin challenge therefore should not be used to diagnose NCGS.
authors: Gastrointestinal Unit, Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors: Cristina
authors: C
authors: Bucci
authors: Fabiana
authors: F
authors: Zingone
authors: Ilaria
authors: I
authors: Russo
authors: Ivonne
authors: I
authors: Morra
authors: Raffaella
authors: R
authors: Tortora
authors: Norberto
authors: N
authors: Pogna
authors: Giulia
authors: G
authors: Scalia
authors: Paola
authors: P
authors: Iovino
authors: Carolina
authors: C
authors: Ciacci
mesh_terms: D000328:Adult; D001491:Basophils / Q000276:immunology*; D001706:Biopsy; D004386:Duodenum / Q000473:pathology; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005903:Gliadin / Q000276:immunology*; D005983:Glutens / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D007413:Intestinal Mucosa / Q000473:pathology; D007558:Italy; D008286:Malabsorption Syndromes / Q000175:diagnosis* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014908:Triticum
chemical_list: D005983:Glutens; D005903:Gliadin
keywords: AGA; Allergy; CD; Diagnostic; Duodenal Immune Response; EMA; FD; GFD; HC; IBS; ICAM-1; IgA; In Vitro Challenge; NCGS; TG2; a-tTG; anti-endomysium antibody; anti-tissue transglutaminase antibody; antigliadin antibodies; celiac disease; free diet; gluten-free diet; healthy control; immunoglobulin A; intercellular cell adhesion molecule-1; irritable bowel syndrome; nonceliac gluten sensitive; transglutaminase 2