ArticleThe Journal of experimental medicine2012
Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 260 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Crossover Trial of Purified Gluten and Whole Wheat (Gluten With Amylase-trypsin Inhibitors) as Triggers of Gastrointestinal Symptoms in Patients With Irritable Bowel Syndrome
Double Blind Randomized Clinical Trial in Subjects With Irritable Bowel Syndrome for the Identification of Gluten Sensitivity
Who cites it
260 citing papers in PubMed, 3 syntheses or guidelines pooled it, 621 citations in OpenAlex.
- European Society for the Study of Coeliac Disease 2025 Updated Guidelines on the Diagnosis and Management of Coeliac Disease in Adults. Part 1: Diagnostic Approach.United European gastroenterology journal · 2025Guideline
- European Consensus on Functional Bloating and Abdominal Distension-An ESNM/UEG Recommendations for Clinical Management.United European gastroenterology journal · 2025Guideline
- Efficacy of the gluten free diet in the management of functional gastrointestinal disorders: a systematic review on behalf of the Italian Society of Paediatrics.Italian journal of pediatrics · 2019Pooled it
- Impact of Acute and Sub-Acute Gluten Exposure on Gastrointestinal Symptoms and Psychological Responses in Non-Coeliac Gluten Sensitivity: A Randomised Crossover Study.United European gastroenterology journal · 2025Trial
- Effects of Gluten on Gut Microbiota in Patients with Gastrointestinal Disorders, Migraine, and Dermatitis.Nutrients · 2024Trial
- Trial
- Phenotypic shift of small intestinal intra-epithelial type 1 innate lymphoid cells in celiac disease is associated with enhanced cytotoxic potential.Clinical and experimental immunology · 2020Trial
- Trial
- Exposure to Different Amounts of Dietary Gluten in Patients with Non-Celiac Gluten Sensitivity (NCGS): An Exploratory Study.Nutrients · 2019Trial
- Trial
- Epitope-specific immunotherapy targeting CD4-positive T cells in coeliac disease: two randomised, double-blind, placebo-controlled phase 1 studies.The lancet. Gastroenterology & hepatology · 2017Trial
- Heterologous Expression and Immunoreactivity of Wheat Amylase-Trypsin Inhibitors.International journal of molecular sciences · 2026Article
- Dietary Adjuvanticity in the Modern Plant Exposome: Implications for Immune-Mediated Inflammatory Diseases.Nutrients · 2026Review
- Refractory Celiac Disease: Nutritional Failure, Immune Dysregulation, and Lymphomagenesis.Nutrients · 2026Review
- Visceral Obesity and Its Complications: The Role of Bioelectrical Impedance Analysis in Longevity Medicine.Metabolites · 2026Review
- Observational
- In Vitro TLR4 Stimulating Bioactivities of Amylase/Trypsin-Inhibitors from Wheat (Foods (Basel, Switzerland) · 2026Article
- Amylase/trypsin inhibitors (ATIs) levels in wheat event IND-ØØ412-7 are similar to non-transgenic wheat.Transgenic research · 2026Article
- Potential of Quantitative α-Amylase or Trypsin Inhibition by Refined and Whole Wheat and Einkorn Using High-Performance Thin-Layer Chromatography-NanoGIT versus Conventional Spectrophotometry.Journal of agricultural and food chemistry · 2026Article
- From gluten to therapeutics: molecular mechanisms of celiac disease and emerging alternatives to the gluten-free diet.Frontiers in pharmacology · 2026Review
200 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 4 countries.
Funding
Abstract
Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac disease. Specifically, the storage proteins of these cereals (gluten) elicit an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. This well-defined role of adaptive immunity contrasts with an ill-defined component of innate immunity in celiac disease. We identify the α-amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4-MD2-CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients' biopsies. Mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.