This work involved a study of gene expression in celiac disease. The prevalence of celiac disease (MC) seems to be steadily increasing according to the statistics of the last 50 years, alarming fact that suggests the involvement also of environmental causes in addition to trigger role of gluten. There are evidences of the existence of predisposing genetic factors such as certain alleles of HLA class II molecules and other gene variants that affect tight junction genes PARD3 and MAGI2. The only treatment available today is the gluten-free diet. However, this does not solve the situation in a fraction of patients and thus need to be other factors involved in the pathogenesis of the disease, not yet identified. The gene expression studies can make an important contribution to identify genes and pathways altered in the MC, not yet known to be associated with the disease. Furthermore, since at the level of the intestinal mucosa occur those of recognition phenomena which lead to tolerance to non-self molecules, the hypothesis that a variation of the permeability of the intestinal barrier can alter the recognition mechanisms, which would lead as a consequence to an increased immune response and contribute to the pathogenesis, has been advanced. This work has identified several clusters of differentially expressed genes and metabolic pathways concerned in celiac disease patients compared to healthy ones: the data are in agreement with previous works, confirming certain hypotheses but further investigations are needed to have a clearer picture of this disease.
Questo lavoro di tesi ha riguardato uno studio di espressione genica nella malattia celiaca. La prevalenza del morbo celiaco (MC) sembra essere in costante aumento secondo i dati statistici degli ultimi 50 anni, dato allarmante che suggerisce il coinvolgimento anche di cause ambientali oltre al fattore scatenante costituito dal glutine. Ci sono evidenze dell’esistenza di fattori genetici predisponenti quali ad esempio determinati alleli HLA di classe II e altre varianti geniche che interessano i geni delle giunzioni strette PARD3 e MAGI2. L’unica terapia ad oggi disponibile è la dieta senza glutine. Tuttavia questa non risolve la situazione in una frazione di malati: quindi devono esistere altri fattori coinvolti nella patogenesi della malattia, non ancora individuati. Gli studi di espressione genica possono dare un contributo importante per individuare geni e vie metaboliche alterati nella MC, non ancora noti per essere associati alla malattia. Inoltre, dal momento che a livello della mucosa intestinale avvengono quei fenomeni di riconoscimento che portano alla tolleranza verso molecole non self, è stata avanzata l’ipotesi che una variazione della permeabilità della barriera intestinale possa alterare i meccanismi di riconoscimento, che porterebbe come conseguenza a un’aumentata risposta immunitaria e contribuire alla patogenesi. Questo lavoro ha individuato diversi cluster di geni differenzialmente espressi nei soggetti celiaci rispetto a quelli sani, e le vie metaboliche interessate: i dati sono in accordo con lavori precedenti, confermando alcune ipotesi ma sono necessari ulteriori indagini per avere un quadro più chiaro di questa malattia.
Indagine sulla eziopatogenesi della malattia celiaca tramite l'analisi del trascrittoma delle cellule mononucleate del sangue periferico.
TORNABENE, IVAN, IGNAZIO
2015/2016
Abstract
This work involved a study of gene expression in celiac disease. The prevalence of celiac disease (MC) seems to be steadily increasing according to the statistics of the last 50 years, alarming fact that suggests the involvement also of environmental causes in addition to trigger role of gluten. There are evidences of the existence of predisposing genetic factors such as certain alleles of HLA class II molecules and other gene variants that affect tight junction genes PARD3 and MAGI2. The only treatment available today is the gluten-free diet. However, this does not solve the situation in a fraction of patients and thus need to be other factors involved in the pathogenesis of the disease, not yet identified. The gene expression studies can make an important contribution to identify genes and pathways altered in the MC, not yet known to be associated with the disease. Furthermore, since at the level of the intestinal mucosa occur those of recognition phenomena which lead to tolerance to non-self molecules, the hypothesis that a variation of the permeability of the intestinal barrier can alter the recognition mechanisms, which would lead as a consequence to an increased immune response and contribute to the pathogenesis, has been advanced. This work has identified several clusters of differentially expressed genes and metabolic pathways concerned in celiac disease patients compared to healthy ones: the data are in agreement with previous works, confirming certain hypotheses but further investigations are needed to have a clearer picture of this disease.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/22114