Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet

Liberto, Diana Di; Mansueto, Pasquale; D’Alcamo, Alberto; Pizzo, Marianna Lo; Presti, Elena Lo; Geraci, Girolamo; Fayer, Francesca; Guggino, Giuliana; Iacono, Giuseppe; Dieli, Francesco; Carroccio, Antonio

doi:10.1038/ctg.2016.35

Cited by 35 publications

(30 citation statements)

References 43 publications

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“…Lower frequencies of NKp44 + ILCs have previously been reported in other gastrointestinal diseases, including ileal lamina propria ILC3s in inflammatory bowel disease (IBD) and rectal mucosal ILC1s in non‐celiac wheat sensitivity (NCWS) , but the reason for attrition of NKp44 + ILCs has not been explored. We observed a marked decrease in NKp44 + ILCs in ACD (and RCD I).…”

Section: Discussionmentioning

confidence: 99%

Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential

Uhde

Bunin

et al. 2020

Clinical &Amp; Experimental Immunology

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The small intestinal (SI) epithelium harbors a heterogeneous population of lymphocytes that mediate mucosal damage and repair in celiac disease (CD). The composition and roles of human proximal SI intra-epithelial innate lymphoid cells (ILCs), and their alterations in CD, are not well understood. We report that duodenal intra-epithelial ILCs predominantly consist of natural killer (NK)p44 + CD127 − cytotoxic ILC1s and NKp44 − CD127 + helper ILC1s, while ILC3s only represent a minor population. In patients with newly diagnosed or active CD (ACD) and refractory CD type 1 (RCD I), the frequency of SI NKp44 + ILCs is decreased, with restoration of NKp44 + ILC frequency observed in patients adhering to a gluten-free diet who show evidence of mucosal healing. Moreover, the frequency of SI NKp44 − ILCs is increased in ACD and RCD I patients and correlates with the severity of villous atrophy and epithelial damage, as assessed by serum levels of fatty acid binding protein 2 (FABP2). We show that the ILC alterations in CD represent a phenotypic shift of cytotoxic ILC1s rather than an increase in helper ILC1s or transdifferentiation of ILC1s to ILC3s, and activation-induced loss of NKp44 by cytotoxic ILC1s is associated with increased interferon (IFN)-γ expression and release of lytic granules. These findings suggest that intra-epithelial NKp44 − CD127 − cytotoxic ILC1s may contribute to mucosal damage in CD.

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Section: Discussionmentioning

confidence: 99%

Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential

Uhde

Bunin

et al. 2020

Clinical &Amp; Experimental Immunology

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“…Several studies have confirmed an immunologic activation in NCG/WS, [5][6][7] however, it is not known whether this is a definitive condition. 8,9 Our data show that approximately 74% of 200 patients had remained on a strict wheat-free diet for a median time of >8 years after a NCG/WS diagnosis, and they all reported that involuntary wheat consumption regularly caused symptoms.…”

Section: Discussionmentioning

confidence: 99%

Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up

Carroccio

D’Alcamo²,

Iacono

et al. 2017

Gastroenterology

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We investigated how many patients with a diagnosis of nonceliac wheat sensitivity (NCWS) still experienced wheat sensitivity after a median follow-up time of 99 months. We collected data from 200 participants from a previous study of NCWS, performed between July and December 2016 in Italy; 148 of these individuals were still on a strict wheatfree diet. In total, 175 patients (88%) improved (had fewer symptoms) after a diagnosis of NCWS; 145 of 148 patients who adhered strictly to a gluten-free diet (98%) had reduced symptoms, compared with 30 of 52 patients who did not adhere to a gluten-free diet (58%) (P < .0001). Of the 22 patients who repeated the double-blind, placebocontrolled challenge, 20 reacted to wheat. We conclude that NCWS is a persistent condition. Clinicaltrials.gov registration number: NCT02823522.

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“…It is conceivable that one of the underlying explanations for this finding in functional dyspepsia is food intolerance and wheat may play a role 36 . A limited role of the adaptive immune system has also been proposed, with increased interferon‐γ‐producing type 1 innate lymphoid cells demonstrated in the rectal mucosa of NCG/WS patients in response to wheat challenge when compared with IBS controls 37 . Despite these early reports, there are still no clearly accepted pathological hallmarks of NCG/WS, nor are there any serological tests or associated enzyme deficiencies, making diagnosis of this syndrome difficult and reliant on a cumbersome dietary trial 21 …”

Section: Pathogenesismentioning

confidence: 99%

Non‐coeliac gluten or wheat sensitivity: emerging disease or misdiagnosis?

Potter

Walker

Talley

2017

Medical Journal of Australia

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Non-coeliac gluten or wheat sensitivity (NCG/WS) is a condition characterised by adverse gastrointestinal and/or extra-intestinal symptoms associated with the ingestion of gluten- or wheat-containing foods, in the absence of coeliac disease or wheat allergy. Up to one in 100 people in Australia may have coeliac disease but many more report adverse gastrointestinal and/or extra-intestinal symptoms after eating wheat products. In the absence of validated biomarkers, a diagnosis of NCG/WS can only be made by a double-blind, placebo-controlled, dietary crossover challenge with gluten, which is difficult to apply in clinical practice. Of people self-reporting gluten or wheat sensitivity, only a small proportion (16%) will have reproducible symptoms after a blinded gluten challenge of gluten versus placebo in a crossover dietary trial and fulfil the current consensus criteria for a diagnosis of NCG/WS. A wide range of symptoms are associated with NCG/WS, including gastrointestinal, neurological, psychiatric, rheumatological and dermatological complaints. The pathogenesis of NCG/WS is not well understood, but the innate immune system has been implicated, and there is overlap with coeliac disease and the functional gastrointestinal disorders (irritable bowel syndrome and functional dyspepsia). Identification of NCG/WS is important as gluten-free diets carry risks, are socially restricting and are costlier than regular diets.

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Predominance of Type 1 Innate Lymphoid Cells in the Rectal Mucosa of Patients With Non-Celiac Wheat Sensitivity: Reversal After a Wheat-Free Diet

Cited by 35 publications

References 43 publications

Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential

Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential

Persistence of Nonceliac Wheat Sensitivity, Based on Long-term Follow-up

Non‐coeliac gluten or wheat sensitivity: emerging disease or misdiagnosis?

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