Celiac disease: How complicated can it get?

Article (PDF Available)inImmunogenetics 62(10):641-51 · October 2010with40 Reads
DOI: 10.1007/s00251-010-0465-9 · Source: PubMed
Abstract
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.
4 Figures
    • "Gluten comprises the proline-and glutamine-rich proteins of wheat, barley, rye, and oat. However, a recent study revealed that oats can be safely consumed by individuals with DH [59][60][61], likely because (1) compared with the gluten-like molecules in the other cereals, those in oats have only two antigenic sequences, and (2) the amount of gluten in oats is much lower than that in the other cereals [62]. Because improvements in DH symptoms related to GFD adherence require a long period-months to years-to occur, patients are usually prescribed dapsone (25-150 mg/day) for fast control of pruritus and blister formation [63]. "
    [Show abstract] [Hide abstract] ABSTRACT: Dermatitis herpetiformis (DH) is an autoimmune bullous disease characterized by intensely pruritic, chronic, and recurrent vesicles on extensor surfaces such as the elbows, knees, and buttocks. The collection of neutrophils at the papillary tips is the typical histopathological finding, and a characteristic diagnostic feature is granular immunoglobulin A deposition in the papillary dermis by direct immunofluorescence. DH is closely associated with gluten sensitive enteropathy and is considered a cutaneous manifestation of gluten sensitivity; i.e., an extra-intestinal presentation of celiac disease. Gluten free diet is the first-line therapy for patients with DH and dapsone is also effective. DH preferentially affects Caucasians who carry human leukocyte antigen (HLA)-DQ2 or HLA-DQ8. The major autoantigen is epidermal transglutaminase. This review focuses on the confirmedfeatures of DH and our recent findings specific to DH in Japanese patients.
    Full-text · Article · Dec 2016 · Italian Journal of Pediatrics
    • "na komórkach dendrytycznych i makrofagach. DPG prezentowane przez APC aktywują pomocnicze limfocyty T CD4 + , co prowadzi do wzmożonej syntezy cytokin prozapalnych, przede wszystkim interferonu gamma (INF-γ) [14] oraz aktywacji innych czynników prozapalnych , w tym metaloproteinaz i rozwinięcia przewlekłego procesu zapalnego jelita cienkiego, objawiającego się przerostem krypt i stopniowym skróceniem kosmków jelitowych, aż po ich zanik. i γδ oraz większości komórek NK [18, 19]dendrytyczna ; Th CD4+ – limfocyt pomocniczy; IEL – limfocyt śródepitelialny; Limf B – limfocyt B; anty-tTG2 – przeciwciała przeciwko transglutaminazie typu 2 oraz znacznie zróżnicowany obraz kliniczny. "
    [Show abstract] [Hide abstract] ABSTRACT: Streszczenie Celiakia (CD) to jedna z najczęstszych chorób o podłożu autoimmunizacyjnym, będąca przyczyną zaburzeń zdrowotnych około 1% populacji. Choroba dotychczas kojarzona z okresem wieku dziecięcego obecnie równie często rozpoznawana jest u pacjentów doro-słych. W ostatnich dekadach obserwuje się również zmianę przebiegu klinicznego w kierunku postaci subklinicznych i nietypowych z dominacją objawów spoza przewodu pokarmowego. W 2012 roku eksperci ESPGHAN (ang. European Society for Pediatric Gastroen-terology, Hepatology and Nutrition) zaktualizowali wytyczne, które podkreślają znaczenie testów serologicznych oraz genetycznych w diagnostyce i badaniach przesiewowych w grupach ryzyka CD. Zgodnie z aktualnymi rekomendacjami badania serologiczne powinny być wykonywane w pierwszej kolejności, zaś badanie histopatologiczne przestało spełniać rolę złotego standardu i w uzasadnionych przypadkach może być pomijane. Dlatego też znaczenie diagnostów laboratoryjnych w procesie diagnostycznym CD znacznie wzrosło w ostatnich latach. W pracy opisano etiopatogenezę, postaci kliniczne CD oraz przedstawiono postępowanie diagnostyczne zgodne z obowiązującymi rekomendacjami. Summary Coeliac disease (CD) is one of the most frequent autoimmune illnesses, causing health disorders about 1% of the population. The disease previously associated with the childhood now as often is diagnosed in adult patients. In recent decades, a change the clinical course towards subclinical and atypical types with dominance of symptoms outside of the gastrointestinal tract has been observed. In 2012 ESPGHAN (European Society for Pediatric Gastroenterology, Hepatology and Nutrition) experts actualized guidelines which emphasized importance of serological and genetic tests in CD diagnosis and the screening in risk groups. According to current guidelines serological tests should be the first diagnostic test, whereas the histopathological examination ceased to act as the golden standard and in appropriate cases may be omitted. Therefore, the relevance of laboratory diagnosticians in CD diagnostic process has increased significantly in recent years. In presented paper an etiopathogenesis, clinical forms of CD and diagnostic procedures in accordance with existing recommendations were described. Słowa kluczowe: badania przesiewowe, celiakia, przeciwciała przeciw deaminowanym peptydom gliadyny, przeciwciała przeciwen-domyzjalne, przeciwciała przeciw transglutaminazie tkankowej.
    Full-text · Article · Oct 2016 · Italian Journal of Pediatrics
    • "Regarding feeding patterns in the first year of life, recent studies have failed to show an impact of breastfeeding duration or timing of gluten introduction on disease development, whereas the data from Sweden point to a possible role of high amount of gluten ingested during the first year of life. All these elements have been integrated by Koning [7] in an attractive model according to which the amount of immunogenic gliadin peptides presented by APC, the higher expression of HLA-DQ and, possibly, conditions promoting the induction of inflammatory T cell responses, such as a viral infection, may have an impact on the risk of CD [27]. Prevention strategies could be implemented, particularly in families at-risk, based on theTable 1 Early feeding practice and risk of CD ● It should be considered that data concerning early feeding practices have been obtained from at-risk families (where at least one CD patient was present), and that possible recommendations should apply only to genetically susceptible individuals. "
    [Show abstract] [Hide abstract] ABSTRACT: Celiac Disease (CD) is an immune-mediated systemic disorder elicited by gluten and related prolamines in genetically susceptible individuals and it is the result of the interaction between genetic and environmental factors. Among genetic risk factors, the strongest association is with the HLA class II DQ region; nevertheless at least 39 non-HLA loci are associated with CD. Gluten is the main environmental trigger of the disease. In addition, infant feeding and weaning practices as well as timing of gluten introduction in the diet have been suggested to contribute to CD risk. Furthermore a role for infectious agents and microbiota composition in disease development has also been proposed. Aim of this short review is to discuss the current knowledge on both genetic and environmental risk factors for the development of CD; moreover we will provide a brief overview of the possible strategies that could be envisaged to prevent this condition, at least in the population at-risk.
    Full-text · Article · Aug 2015
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