New Insights into the Pathogenesis of Celiac Disease

Abstract

Celiac disease (CD) is an autoimmune and multisystem gluten-related disorder that causes symptoms involving the gastrointestinal tract and other organs. Pathogenesis of CD is only partially known. It had been established that ingestion of gluten proteins present in wheat and other cereals are necessary for the disease and develops in individuals genetically predisposed carrying the DQ2 or DQ8 human leukocyte antigen haplotypes. In this review, we had pay specific attention on the last discoveries regarding the three cellular components mainly involved in the development and maintenance of CD: T-cells, B-cells, and microbioma. All of them had been showed critical for the interaction between inflammatory immune response and gluten peptides. Although the mechanisms of interaction among overall these components are not yet fully understood, recent proteomics and molecular studies had shed some lights in the pathogenic role of tissue transglutaminase 2 in CD and in the alteration of the intestinal barrier function induced by host microbiota.

The Effect of Gluten-Free Diet on Health and the Gut Microbiota Cannot Be Extrapolated from One Population to Others

“…From all GRD, CD has been the most studied and is currently considered to be the most common chronic enteropathy worldwide [ 14 ]. In people with CD, a significantly enhanced autoantibody response to the transglutaminase 2 (TG2) enzyme, also known as tissue transglutaminase (tTG), is a hallmark of the pathogenic process that primarily affects the architecture of the enterocyte lining of the small intestine [ 15 ] but can also affect other organs such as the liver, kidney, lymph nodes and muscles [ 16 , 17 ].…”

Pathogenesis of Celiac Disease and Other Gluten Related Disorders in Wheat and Strategies for Mitigating Them

“…Its upregulation due to gluten exposure disrupts the integrity of tight junctions between epithelial cells of small intestine and increases the paracellular movement of protease resistant gluten fragments (93,94). As a result, the undigested gluten peptide fragments pass through epithelial barrier of small intestine and enter lamina propria where these are deaminated by the enzyme tissue transglutaminase (TG2) which converts glutamine to glutamate thereby imparting negative charge to gluten fragments (95). Further, the activity of the enzyme TG2 is dependent on spacing between glutamine and proline.…”

“…Deamination of gluten peptides by TG2 is the key pathogenic event that increases gliadin immunogenicity in CD and enhances the severity of disease (97). TG2 plays an important role in CD pathogenesis and anti-TG2 antibodies are used as the markers for CD diagnosis (95). The enzyme TG2 is located on the brush border epithelia of the small intestine or in extracellular space of sub-epithelial region (98).…”

“…The recognition and binding of T-cell receptors to specific HLAgliadin complexes lead to the production of high levels of proinflammatory cytokines dominated mainly by interferon (IFN)γ (65, 101, 102). These cytokines either induce T-helper 1 cells to produce IL-15 and IL-21 which result in the activation of cytotoxic CD8+ intra epithelial lymphocytes (IELs) and promote CD8+ T-cell cytotoxic activity and contributes to intestinal lesions, inflammation and intestinal mucosal damage (95,103) or T-helper 2 cells to cause B-lymphocytes differentiation for the secretion of anti-gliadin, anti-TG2, and anti-endomysium (EM) antibodies which are considered as the key characteristics of active CD (65, 104). An increased density of CD8+ IELs is also considered as an important characteristic of CD (90,105).…”

Quantitative assessment of nutrition and nutritional status of patients with celiac disease aged 13–18

“…Celiac diagnosis is based on specific serological tests, including antibodies against endomysium and anti-transglutaminase tissue [6,15]. Serological tests are used not only for diagnosis but also for subsequent monitoring of compliance with a gluten-free diet [16].…”