Immune mechanisms have been implicated in nonceliac gluten sensitivity (NCGS), a condition characterized by intestinal and/or extraintestinal symptoms caused by the ingestion of gluten in non-celiac/non-wheat allergic individuals.
We investigated innate and adaptive immunity in self-reported NCGS versus celiac disease (CD).
In the supernatants of ex vivo-cultured duodenal biopsies from 14 self-reported NCGS patients, 9 untreated and 10 treated CD patients, and 12 controls we detected innate cytokines – interleukin (IL)-15, tumor necrosis factor-α, IL-1β, IL-6, IL-12p70, IL-23, IL-27, IL-32α, thymic stromal lymphopoietin (TSLP), IFN-α-, adaptive cytokines – interferon (IFN)-γ, IL-17A, IL-4, IL-5, IL-10, IL-13-, chemokines – IL-8, CCL1, CCL2, CCL3, CCL4, CCL5, CXCL1, CXCL10-, granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF).
Mucosal innate and adaptive cytokines, chemokines and growth factors did not differ between self-reported NCGS, treated CD and controls. On the contrary, IL-6, IL-15, IL-27, IFN-α, IFN-γ, IL-17A, IL-23, G-CSF, GM-CSF, IL-8, CCL1 and CCL4 were significantly higher in untreated CD than in self-reported NCGS, treated CD and controls, while TSLP was significantly lower in untreated CD than in self-reported NCGS, treated CD and controls.
In our hands, patients with self-reported NCGS showed no abnormalities of the mucosal immune response.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Digestive and Liver Disease
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Spectrum of gluten-related disorders: consensus on new nomenclature and classification.BMC Medicine. 2012; 10: 13
- Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders.Nutrients. 2013; 5: 3839-3853
- The Oslo definitions for coeliac disease and related terms.Gut. 2013; 62: 43-52
- Regulation of the T helper cell type 1 transcription factor T-bet in coeliac disease mucosa.Gut. 2004; 53: 1090-1095
- Characterization of IL-17A-producing cells in celiac disease mucosa.Journal of Immunology. 2010; 184: 2211-2218
- Epithelium derived interleukin 15 regulates intraepithelial lymphocyte Th1 cytokine production, cytotoxicity, and survival in coeliac disease.Gut. 2006; 55: 469-477
- Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease.Lancet. 2003; 362: 30-37
- Nonceliac gluten sensitivity.Gastroenterology. 2015; 148: 1195-1204
- Self-reported gluten sensitivity: an international concept in need of consensus?.American Journal of Gastroenterology. 2014; 109: 1498-1499
- Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity.American Journal of Gastroenterology. 2013; 108: 842-850
- An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity.BMC Medicine. 2014; 12: 85
- A UK study assessing the population prevalence of self-reported gluten sensitivity and referral characteristics to secondary care.European Journal of Gastroenterology and Hepatology. 2014; 26: 33-39
- Coeliac disease.Lancet. 2009; 379: 1480-1493
- Coeliac disease.Journal of Clinical Pathology. 2005; 58: 573-574
- Small amounts of gluten in subjects with suspected nonceliac gluten sensitivity: a randomized, double-blind, placebo-controlled, cross-over trial.Clinical Gastroenterology and Hepatology. 2015; 13: 1604-1612
- Endomysial antibody-negative coeliac disease: clinical characteristics and intestinal autoantibody deposits.Gut. 2006; 55: 1746-1753
- Transforming growth factor beta signalling and matrix metalloproteinases in the mucosa overlying Crohn's disease strictures.Gut. 2009; 58: 777-789
- Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells.Nature Immunology. 2005; 6: 507-514
- Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease.Gut. 2001; 48: 425-429
- Abnormal thymic stromal lymphopoietin expression in the duodenal mucosa of patients with coeliac disease.Gut. 2015; https://doi.org/10.1136/gutjnl-2014-308876
- Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.American Journal of Gastroenterology. 2011; 106: 508-514
- Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity.BMC Medicine. 2011; 9: 23
- A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function.Gastroenterology. 2013; 144: 903-911
- Differential mucosal IL-17 expression in two gliadin-induced disorders: gluten sensitivity and the autoimmune enteropathy celiac disease.International Archives of Allergy and Immunology. 2010; 152: 75-80
- Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity.Clinical Gastroenterology and Hepatology. 2013; 11: 1294-1299
- Chemokines in inflammatory bowel diseases.Digestive Diseases. 2010; 28: 386-394
- Colony-stimulating factors in inflammation and autoimmunity.Nature Reviews Immunology. 2008; 8: 533-544
- Similar IL-5, IL-3, and GM-CSF syntheses by eosinophils in the jejunal mucosa of patients with celiac disease and dermatitis herpetiformis.Clinical Immunology and Immunopathology. 1998; 88: 14-21
- Increased expression of mucosal addressin cell adhesion molecule 1 in the duodenum of patients with active celiac disease is associated with depletion of integrin alpha4beta7-positive T cells in blood.Human Pathology. 2009; 40: 699-704
- Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity.American Journal of Gastroenterology. 2012; 107: 1898-1906
- Randomised clinical study: gluten challenge induces symptom recurrence in only a minority of patients who meet clinical criteria for non-coeliac gluten sensitivity.Alimentary Pharmacology and Therapeutics. 2015; 42: 968-976
- Cryptic genetic gluten intolerance revealed by intestinal antitransglutaminase antibodies and response to gluten-free diet.Gut. 2011; 60: 1487-1493
- A comparison of symptoms after the consumption of milk or lactose-hydrolyzed milk by people with self-reported severe lactose intolerance.New England Journal of Medicine. 1995; 333: 1-4
- A double-blind study of symptom provocation to determine food sensitivity.New England Journal of Medicine. 1990; 323: 429-433
- Nonceliac gluten sensitivity: sense or sensibility?.Annals of Internal Medicine. 2012; 156: 309-311
- Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4.Journal of Experimental Medicine. 2012; 209: 2395-2408
- Behavioral effects of food-derived opioid-like peptides in rodents: implications for schizophrenia?.Pharmacology Biochemistry and Behavior. 2015; 134: 70-78
- Other Dietary Confounders: FODMAPS et al..Digestive Diseases. 2015; 33: 269-276
- Alimentary exorphin actions on motility and hormonal secretion of gastrointestinal tract.in: Fraioli F. Isidori A. Mazzetti M. Opioid peptides in periphery. Elsevier Science Publisher, Amsterdam1984: 243-247
- H2 excretion after ingestion of complex carbohydrates.Gastroenterology. 1987; 92: 383-389
- The effect of gluten on intestinal fermentation, gastric and gallbladder emptying in healthy volunteers.Digestive and Liver Disease. 2015; 47: 751-756
- No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.Gastroenterology. 2013; 145: 320-328
Published online: April 26, 2016
Accepted: March 30, 2016
Received: December 13, 2015
© 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.