Celiac disease påverkar längd
The present review is timely and provides a thorough appraisal of various aspects characterizing celiac disease. Celiac disease CD is an autoimmune condition characterized by a specific serological and histological profile triggered by gluten ingestion in genetically predisposed individuals [ 1 ]. CD is one of the most common autoimmune disorders, with a reported prevalence of 0.
A major milestone in the history of celiac disease was the identification of tissue transglutaminase as the autoantigen, thereby confirming the autoimmune nature of this disorder. Studies from our group and others have shown that gliadin can cause an immediate and transient increase in intercellular tight junction permeability of intestinal epithelial cells [ 23 , 24 ] Fig. This effect has been linked to the release of zonulin, a family of molecules that increases paracellular permeability by causing tight junction disassembly [ 29 , 30 , 31 ].
The relevance of these additional genes in conferring genetic risk for CD is rather limited, but they may lead to the discovery of key pathways potentially involved in disease pathogenesis. With breakthroughs in the role of the gut microbiological ecosystem [ 17 ] in dictating the balance between tolerance and immune response leading to autoimmunity, this hypothesis is under scrutiny.
A major drawback in CD research has been the lack of a reliable and reproducible animal model, with the possible exception of the Irish setter dog, which may develop a gluten-related disease [ 15 ]. The transferrin receptor CD71, normally expressed on the basolateral side of enterocytes, is overexpressed on the luminal side of the intestinal epithelium in CD patients during the acute phase of the disease, leading to an apical-to-basal retrotranscytosis of gliadin peptides complexed with secretory IgA [ 47 ].
Celiaki följdsjukdomar
Gliadin enhances zonulin-dependent increased gut paracellular permeability irrespective of disease status [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. The hygiene hypothesis argues that the rising incidence of many autoimmune diseases may partially be the result of lifestyle and environmental changes that have reduced our exposure to pathogens. These two characteristics could help in breaking the tolerance to this food antigen, when the immune system is activated, as can happen during an enteric infection.
Partially digested gliadin fragments interact with chemokine receptor 3 on the apical side of epithelium 1 inducing a myeloid differentiation primary response dependent release of zonulin 2. However, these hypotheses have not been confirmed and the real cause of the risk in CD diagnoses remains unknown. This has been mainly attributed to the greater availability of sensitive and specific screening tests, which allow identification of the risk groups for CD and led to a significant raise in diagnoses worldwide [ 2 , 3 , 4 , 5 ].
The involvement of the paracellular pathway for gluten trafficking in the lamina propria has also been corroborated by genetic studies identifying an association of some tight junction genes with CD [ 42 , 43 , 44 ]. Gluten is the general term for alcohol-soluble proteins present in various cereals, including wheat, rye, barley, spelt, and kamut [ 1 ].
Celiac disease remains a challenging condition because of a steady increase in knowledge tackling its pathophysiology, diagnosis, management, and possible therapeutic options. The identification of alternative or complementary treatments to the gluten-free diet brings hope for patients unavoidably burdened by diet restrictions.
As with many other autoimmune diseases, we have witnessed an epidemic of CD, questioning the previous paradigm that gluten is the only key element dictating the onset of the disease in genetically at-risk subjects. In addition, the quality of gluten itself might also play a contributory role. Nevertheless, new technologies pertinent to human gut biology and immunology are opening unprecedented opportunities for major research breakthroughs.
Currently, the only treatment for celiac disease is a life-long, strict gluten-free diet leading to improvement in quality of life, ameliorating symptoms, and preventing the occurrence of refractory celiac disease, ulcerative jejunoileitis, and small intestinal adenocarcinoma and lymphoma. We have also identified two alpha-gliadin motifs that can modulate the intestinal barrier function by binding to chemokine receptor 3, with subsequent zonulin release that causes disassembly of the interepithelial tight junction complex [ 41 ].
This retrotranscytosis of secretory IgA—gliadin complexes protects gliadin fragments from lysosomal degradation and promotes the entry of harmful gliadin peptides into the intestinal lamina propria [ 47 ], thereby perpetuating intestinal inflammation initiated by the paracellular passage of these peptides Fig.
Because of their resistance, the gluten immunogenic peptides GIP can cross the defective epithelial lining, reach the blood stream thus extending the inflammatory process , and finally be excreted with the urine [ 48 ]. Remaining challenges include obtaining a better understanding of still-unclear phenotypes such as slow-responsive, potential minimal lesions and seronegative celiac disease. This multifaceted clinical presentation leads to several phenotypes, i.
CD prevalence is increasing in Western countries.
Celiac disease: a comprehensive current review
The final product of this partial digestion is a mix of peptides that can trigger host responses increased gut permeability and innate and adaptive immune response that closely resemble those instigated by the exposure to potentially harmful microorganisms [ 25 , 26 , 27 , 28 ]. Moreover, gluten is one of the few digestion-resistant proteins consumed chronically in significant quantities and is constituted by several non-digestible immunogenic peptides.
Between the years and , CD prevalence increased 5-fold in the US, for reasons that are currently unknown [ 14 ]. Celiac disease pathogenesis. Regardless of whether autoimmune diseases are due to too much or too little exposure to microorganisms, it is generally accepted that adaptive immunity and imbalance between T helper 1 and 2 cell responses are key elements of the pathogenesis of the autoimmune process.
Gliadins, key components of gluten, are complex proteins unusually rich in prolines and glutamines and are not completely digestible by intestinal enzymes [ 24 ]. Metrics details. There is solid evidence that gluten can also cross the intestinal barrier through the transcellular pathway once tolerance to gluten has been broken [ 45 , 46 ]. In this article, we aimed to provide a thorough review on the multifaceted features of CD spanning from its epidemiological, pathogenetic, clinical, and diagnostic aspects to therapeutic strategies using a practical approach in order to help general practitioners, internal medicine physicians, and gastroenterologists in their clinical practice.
Peer Review reports. Indeed, the production of new grain variants due to technological rather than nutritional reasons may have influenced the observed increase in the number of CD diagnoses in recent years [ 4 , 5 ].