Celiac disease: How complicated can it get?

Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, RC Leiden, The Netherlands.
Immunogenetics (Impact Factor: 2.23). 10/2010; 62(10):641-51. DOI: 10.1007/s00251-010-0465-9
Source: PubMed


In the small intestine of celiac disease patients, dietary wheat gluten and similar proteins in barley and rye trigger an inflammatory response. While strict adherence to a gluten-free diet induces full recovery in most patients, a small percentage of patients fail to recover. In a subset of these refractory celiac disease patients, an (aberrant) oligoclonal intraepithelial lymphocyte population develops into overt lymphoma. Celiac disease is strongly associated with HLA-DQ2 and/or HLA-DQ8, as both genotypes predispose for disease development. This association can be explained by the fact that gluten peptides can be presented in HLA-DQ2 and HLA-DQ8 molecules on antigen presenting cells. Gluten-specific CD4(+) T cells in the lamina propria respond to these peptides, and this likely enhances cytotoxicity of intraepithelial lymphocytes against the intestinal epithelium. We propose a threshold model for the development of celiac disease, in which the efficiency of gluten presentation to CD4(+) T cells determines the likelihood of developing celiac disease and its complications. Key factors that influence the efficiency of gluten presentation include: (1) the level of gluten intake, (2) the enzyme tissue transglutaminase 2 which modifies gluten into high affinity binding peptides for HLA-DQ2 and HLA-DQ8, (3) the HLA-DQ type, as HLA-DQ2 binds a wider range of gluten peptides than HLA-DQ8, (4) the gene dose of HLA-DQ2 and HLA-DQ8, and finally,(5) additional genetic polymorphisms that may influence T cell reactivity. This threshold model might also help to understand the development of refractory celiac disease and lymphoma.

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    • "The proteins of these cereals can be classified , according to their solubility in alcohol and acids , as prolamins and glutenins, which are partially resistant to human proteases. When ingested by coeliac-disease patients, several immunogenic gluten peptides are generated, activating the immune system through multiple cellular channels and resulting in premature ageing of the mucus enterocytes that cover the intestinal tract (Schuppan et al., 2009; Di Sabatino and Corazza, 2009; Tjon et al., 2010). "
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    ABSTRACT: Quinoa (Chenopodium quinoa Willd.) is an amaranthaceous plant that has been recognized for centuries as an important food crop in the South American Andes. Its grains are highly nutritious; with a high protein and bioactive compound content that surpasses traditional cereal grains in terms of biological value. Quinoa is a nutritionally well-balanced food product with multiple functions associated with the reduction of chronic disease risk, thanks to its anti-oxidant, anti-inflammatory, immunomodulatory, anticarcinogenic and other properties. This chapter provides an up-to-date overview of the nutraceutical perspectives of quinoa, based on various scientific studies of its biological properties and functional applications beneficial to human health.
    The state of the world's quinoa, Edited by Didier Bazile, Daniel Bertero, Carlos Nieto, 03/2015: chapter Nutraceutical Perspectives of Quinoa: Biological Properties and Functional Applications: pages 286-299; Regional Office for Latin America and Caribbean at Food and Agriculture Organization (FAO).
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    • "Due to presence of glutamine and proline in the amino acid sequence, a number of gluten peptides directly bind DQ2 or DQ8 in the binding groove while other peptides require prior modification to enhance binding. The HLA DQ2 and DQ8 receptors preferentially bind peptides with negatively charged amino acids and bulky amino acids at certain anchor residues (Tjon and others 2010). Moreover, tissue-bound transglutaminase selectively deamidates glutamine to create glutamic acid, which allows certain gluten peptides to fit in the binding pockets of HLA DQ2 and DQ8 (van de Wal and others 1998; Arentz- Hansen and others 2000; Vader and others 2002a; Kim and others 2004; Stepniak and others 2005). "
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    ABSTRACT: The role of wheat, and particularly of gluten protein, in our diet has recently been scrutinized. This article provides a summary of the main pathologies related to wheat in the human body, including celiac disease, wheat allergy, nonceliac wheat sensitivity, fructose malabsorption, and irritable bowel syndrome. Differences in reactivity are discussed for ancient, heritage, and modern wheats. Due to large variability among species and genotypes, it might be feasible to select wheat varieties with lower amounts and fewer types of reactive prolamins and fructans. Einkorn is promising for producing fewer immunotoxic effects in a number of celiac research studies. Additionally, the impact of wheat processing methods on wheat sensitivity is reviewed. Research indicates that germination and fermentation technologies can effectively alter certain immunoreactive components. For individuals with wheat sensitivity, less-reactive wheat products can slow down disease development and improve quality of life. While research has not proven causation in the increase in wheat sensitivity over the last decades, modern wheat processing may have increased exposure to immunoreactive compounds. More research is necessary to understand the influence of modern wheat cultivars on epidemiological change.
    Comprehensive Reviews in Food Science and Food Safety 02/2015; 14(3). DOI:10.1111/1541-4337.12129 · 4.18 Impact Factor
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    • "Individuals with pathological responses to wheat are advised to follow the only known treatment at this time, a gluten-free diet (GFD). [18] A GFD has the potential to reverse some of the damages to the gut and other regions of the body. [19] Surprisingly, the growth of the market for gluten free products far exceeds that predicted by the 1-2% prevalence for CeD [20] Some of these purchases may reflect people following a new " fad diet " [21] but there may be additional reasons for the increased sales of gluten-free products. "
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    ABSTRACT: Wheat consumption is increasing worldwide and also increasing is the frequency of celiac disease (CeD), a pathological response to wheat protein (gluten) in genetically susceptible individuals. Non-celiac gluten sensitivity (NCGS) is another, less studied wheat-induced pathology. The treatment for both is a gluten-free diet (GFD). More individuals choose the diet than predicted by the epidemiological 1-2% prevalence. A preliminary survey by questionnaire asked members and attendees of the local gluten information group (GIG) meetings and functions about their diagnostic experiences and symptom levels in order understand the increased demand for gluten-free foods. Same-aged and-sex friends participated as a comparative " control ". Mixed methods were used including content analyses of prose narratives and independent and paired t tests of symptom levels measured with Likert scales. This convenience sample, surveyed in 2011-2012, is mostly female (54 F, 5 M) with an average age of 54.6 ± 2.0 years. Most participants consulted medical professionals with mean time to diagnosis of 7 years determined mostly from " classic " presenting symptoms. Negative biopsies or blood tests and atypical symptoms that overlap other conditions delayed diagnosis. There were 43 and 16 participants with CeD and NCGS, respectively differing little in symptom levels. Self-diagnosis and use of naturopaths account for some of the " excess " individuals. General practitioners should be encouraged to get additional nutrition training and to discuss with patients dietary choices that support wellness and minimize the risk for pathological immune responses. Patients with CeD particularly need support and follow-up in the transition to a GFD.
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