Specific Nongluten Proteins of Wheat Are Novel Target Antigens in Celiac Disease Humoral Response

Huebener, Sina; Tanaka, Charlene K.; Uhde, Melanie; Zone, John J.; Vensel, William H.; Kasarda, Donald D.; Beams, Leilani; Briani, Chiara; Green, Peter H.R.; Altenbach, Susan B.; Alaedini, Armin

doi:10.1021/pr500809b

Cited by 59 publications

(56 citation statements)

References 34 publications

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“…Serum IgG, IgA and IgM antibodies to native gliadin were measured separately by ELISA as previously described,24 26 with the following modification: the secondary antibodies were horseradish peroxidase (HRP)-conjugated anti-human IgG (GE Healthcare), IgA (MP Biomedicals) or IgM (MP Biomedicals). Serum IgG, IgA and IgM antibodies to bacterial flagellin were measured separately using a similar protocol for detecting antibodies to gliadin, with the following modification: plates were coated with a 2 μg/mL solution of highly purified flagellin from Salmonella typhimurium (InvivoGen).…”

Section: Methodsmentioning

confidence: 99%

Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease

Uhde

Ajamian

Caio

et al. 2016

Gut

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192

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ObjectiveWheat gluten and related proteins can trigger an autoimmune enteropathy, known as coeliac disease, in people with genetic susceptibility. However, some individuals experience a range of symptoms in response to wheat ingestion, without the characteristic serological or histological evidence of coeliac disease. The aetiology and mechanism of these symptoms are unknown, and no biomarkers have been identified. We aimed to determine if sensitivity to wheat in the absence of coeliac disease is associated with systemic immune activation that may be linked to an enteropathy.DesignStudy participants included individuals who reported symptoms in response to wheat intake and in whom coeliac disease and wheat allergy were ruled out, patients with coeliac disease and healthy controls. Sera were analysed for markers of intestinal cell damage and systemic immune response to microbial components.ResultsIndividuals with wheat sensitivity had significantly increased serum levels of soluble CD14 and lipopolysaccharide (LPS)-binding protein, as well as antibody reactivity to bacterial LPS and flagellin. Circulating levels of fatty acid-binding protein 2 (FABP2), a marker of intestinal epithelial cell damage, were significantly elevated in the affected individuals and correlated with the immune responses to microbial products. There was a significant change towards normalisation of the levels of FABP2 and immune activation markers in a subgroup of individuals with wheat sensitivity who observed a diet excluding wheat and related cereals.ConclusionsThese findings reveal a state of systemic immune activation in conjunction with a compromised intestinal epithelium affecting a subset of individuals who experience sensitivity to wheat in the absence of coeliac disease.

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Section: Methodsmentioning

confidence: 99%

Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease

Uhde

Ajamian

Caio

et al. 2016

Gut

Self Cite

192

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“…Recently, Huebener and colleagues have analysed the possible involvement of non-gluten proteins as target antigens in celiac disease related humoral response29. Serine-protease inhibitors, alpha-amylase inhibitors, farinins and seed globulins have demonstrated a significant immune response.…”

Section: Discussionmentioning

confidence: 99%

Characterization of globulin storage proteins of a low prolamin cereal species in relation to celiac disease

Gell

Kovács

Veres

et al. 2017

Sci Rep

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Brachypodium distachyon, a small annual grass with seed storage globulins as primary protein reserves was used in our study to analyse the toxic nature of non-prolamin seed storage proteins related to celiac disease. The main storage proteins of B. distachyon are the 7S globulin type proteins and the 11S, 12S seed storage globulins similar to oat and rice. Immunoblot analyses using serum samples from celiac disease patients were carried out followed by the identification of immune-responsive proteins using mass spectrometry. Serum samples from celiac patients on a gluten-free diet, from patients with Crohn’s disease and healthy subjects, were used as controls. The identified proteins with intense serum-IgA reactivity belong to the 7S and 11–12S seed globulin family. Structure prediction and epitope predictions analyses confirmed the presence of celiac disease-related linear B cell epitope homologs and the presence of peptide regions with strong HLA-DQ8 and DQ2 binding capabilities. These results highlight that both MHC-II presentation and B cell response may be developed not only to prolamins but also to seed storage globulins. This is the first study of the non-prolamin type seed storage proteins of Brachypodium from the aspect of the celiac disease.

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“…Huebener et al. () investigated the level and molecular specificity of the antibody response to non‐gluten proteins of wheat in CD. Serum samples from patients and controls were screened for IgG and IgA antibody reactivity to a non‐gluten protein extract from the wheat cultivar Triticum aestivum ‐Butte 86.…”

Section: Celiac Diseasementioning

confidence: 99%

Adverse Reactions to Wheat or Wheat Components

Brouns

Rooy

Shewry

et al. 2019

Comp Rev Food Sci Food Safe

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Wheat is an important staple food globally, providing a significant contribution to daily energy, fiber, and micronutrient intake. Observational evidence for health impacts of consuming more whole grains, among which wheat is a major contributor, points to significant risk reduction for diabetes, cardiovascular disease, and colon cancer. However, specific wheat components may also elicit adverse physical reactions in susceptible individuals such as celiac disease (CD) and wheat allergy (WA). Recently, broad coverage in the popular and social media has suggested that wheat consumption leads to a wide range of adverse health effects. This has motivated many consumers to avoid or reduce their consumption of foods that contain wheat/gluten, despite the absence of diagnosed CD or WA, raising questions about underlying mechanisms and possible nocebo effects. However, recent studies did show that some individuals may suffer from adverse reactions in absence of CD and WA. This condition is called non‐celiac gluten sensitivity (NCGS) or non‐celiac wheat sensitivity (NCWS). In addition to gluten, wheat and derived products contain many other components which may trigger symptoms, including inhibitors of α‐amylase and trypsin (ATIs), lectins, and rapidly fermentable carbohydrates (FODMAPs). Furthermore, the way in which foods are being processed, such as the use of yeast or sourdough fermentation, fermentation time and baking conditions, may also affect the presence and bioactivity of these components. The present review systematically describes the characteristics of wheat‐related intolerances, including their etiology, prevalence, the components responsible, diagnosis, and strategies to reduce adverse reactions.

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Specific Nongluten Proteins of Wheat Are Novel Target Antigens in Celiac Disease Humoral Response

Cited by 59 publications

References 34 publications

Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease

Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease

Characterization of globulin storage proteins of a low prolamin cereal species in relation to celiac disease

Adverse Reactions to Wheat or Wheat Components

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