Gene Expression Profiling in Coeliac Disease Confirmed the Key Role of the Immune System and Revealed a Molecular Overlap with Non-Celiac Gluten Sensitivity

Abstract: Coeliac disease (CeD) is an immune-mediated disorder triggered by the ingestion of glutenand an as yet unidentified environmental factor in genetically predisposed individuals. The diseaseinvolves a major autoimmune component that primarily damages the intestinal mucosa; although, italso has systemic involvement. The Th1 inflammatory response is one of the main events leadingto mucosal damage; although, enterocytes and the innate immune response also participate in thepathological mechanism. In this study, we performed an analysis of the gene expression profile ofthe intestinal mucosa of patients with active disease and compared it with that of patients who donot suffer from gluten-related disorders but report dyspeptic symptoms. This analysis identified1781 differentially expressed (DE) genes, of which 872 were downregulated and 909 upregulated.Gene Ontology and pathway analysis indicated that the innate and adaptive immune response, inparticular the Th1 pathway, are important pathogenetic mechanisms of CeD, while the key cytokinesare IL27, IL21, IL2, IL1b, TNF, CSF2 and IL7, as well as type I (IFNA1, IFNA2) and type II (IFNG)interferons. Finally, the comparison between the DE genes identified in this study and those identifiedin our previous study in the intestinal mucosa of patients with non-celiac gluten sensitivity (NCGS)revealed a high degree of molecular overlap. About 30% of the genes dysregulated in NCGS, mostof which are long non-coding RNAs, are also altered in CeD suggesting that these diseases mayhave a common root (dysregulated long non-coding RNAs) from which they develop towards aninflammatory phenotype of variable degree in the case of CeD and NCGS respectively.