Current concepts of celiac disease pathogenesis

First Department of Medicine, University of Erlangen-Nuernberg, Erlangen, Germany.
Gastroenterology (Impact Factor: 13.93). 08/2000; 119(1):234-42. DOI: 10.1053/gast.2000.8521
Source: PubMed

ABSTRACT Our knowledge of celiac disease pathogenesis has recently made rapid progress. The disorder is now considered the result of a complex interplay of intrinsic (genetic) and variable extrinsic (environmental) factors that explain the wide spectrum of clinical manifestations ranging from asymptomatic to severe malabsorption. Gluten peptides are efficiently presented by celiac disease-specific HLA-DQ2- and HLA-DQ8-positive antigen-presenting cells, and thus drive the immune response, predominantly in the connective tissue of the lamina propria. Tissue transglutaminase, which has been identified as the highly specific endomysial autoantigen, is released from cells during inflammation. It may potentiate antigen presentation by HLA-DQ2 and HLA-DQ8 by deamidating or cross-linking gluten peptides. The result is lamina propria T-cell activation and mucosal transformation by activated intestinal fibroblasts. In the future, manipulation of the gut-associated lymphoid tissue may allow reduced sensitivity or even generate oral tolerance to gluten. Long-standing untreated celiac disease, even if clinically silent, predisposes for other autoimmune diseases. Therefore, population screening for immunoglobulin A antibodies to tissue transglutaminase seems justified.

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Available from: Detlef Schuppan, Nov 26, 2014
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    • "As well as for its rheological properties, there is an increasing interest in studying gluten proteins because they are the main factor causing celiac disease, an autoimmune enteropathy. Besides the consumption of gluten, celiac disease needs a genetic predisposition due to an antigluten T-cell response associated with specific histocompatibility antigens, namely HLA-DQ2.5 and HLA-DQ8, and the loss of the oral tolerance to gluten (Schuppan, 2000). The immune response in celiac subjects is due both to toxic motifs triggering the innate immune system and to epitopes influencing Abbreviations: Fmoc, fluorenylmethoxycarbonyl; HLA, human leukocyte antigen ; HMW, high molecular weight; LC/MS, liquid chromatography/mass spectrometry ; LMW, low molecular weight; tBu, tert-butyl; TIS, triisopropylsilane; TPC, total protein content; Trt, trityl; UPLC, ultra performance liquid chromatography. "
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    ABSTRACT: Gluten proteins are the basis of the rheological properties of wheat derived products, such as bread and pasta. Their particular amino acidic composition (high proline and glutamine content) is responsible for the poor gluten digestibility. Some of the high molecular weight peptides that are generated in the gastrointestinal tract are involved in an autoimmune entheropathy called celiac disease. In this work we compared the amount of peptides containing sequences involved in adaptive and immune responses, which were produced after simulated gastrointestinal digestion of prolamins extracted from different durum wheat varieties and in-bred lines. Peptides containing sequences involved in celiac disease were quantified using an isotopically labeled peptide as internal standard. The results demonstrated a very high variability in the amount of pathogenic peptides produced by different lines, showing a strong contribution of the genetic component. At the same time, the variability in total protein and gluten content was lower; the weak correlation between pathogenic peptides and the amount of gluten proteins gives rise to the possibility of a varietal selection aimed to maintain good rheological properties, but simultaneously reducing the exposure to peptides eliciting an immunological response in celiac predisposed subjects. These varieties might be useful for celiac disease prevention.
    Journal of Cereal Science 01/2013; 59(1). DOI:10.1016/j.jcs.2013.10.006 · 1.94 Impact Factor
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    • "The disease is triggered by consumption of gluten, a group of storage proteins found in wheat, barley, and rye grains, resulting in intestinal inflammation , villous atrophy, and crypt cell hyperplasia, which leads to a significant decrease in intestinal wall surface area. As a consequence, a number of symptoms affect celiac patients, such as diarrhea, weight loss, anemia, and bone disorders (Farrel and Kelly 2002; Green and Cellier 2007; Schuppan 2000; Sollid 2002). It is often assumed that the disease appears only in early childhood; however, evidence has shown that adults can also develop celiac disease (Vilppula et al. 2009). "
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    Functional & Integrative Genomics 06/2012; 12(3):417-38. DOI:10.1007/s10142-012-0287-y · 2.69 Impact Factor
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    • "Gliadins are the alcohol soluble part of gluten with particularly high content of glutamine and proline [32]. Gliadins are only partially digested in the gut comprising peptides which are resistant to digestion [33]. Such digestion-resistant peptides can thus be modified by tTG in two alternative ways that include deamidation and transamidation [34] [35]. "
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    ABSTRACT: Dermatitis herpetiformis (DH) is a rare autoimmune disease linked to gluten sensitivity with a chronic-relapsing course. It is currently considered to be the specific cutaneous manifestation of celiac disease (CD). Both conditions are mediated by the IgA class of autoantibodies, and the diagnosis of DH is dependent on the detection of granular deposits of IgA in the skin. There is an underlying genetic predisposition to the development of DH, but environmental factors are also important. This paper describes these different factors and discusses the known mechanism that lead to the development of skin lesions.
    Clinical and Developmental Immunology 06/2012; 2012:239691. DOI:10.1155/2012/239691 · 2.93 Impact Factor
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