Article

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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