Identification of peculiar gene expression profile in peripheral blood mononuclear cells (PBMC) of celiac patients on gluten free diet

• Published in: PloS one 2018-05, Vol.13 (5), p.e0197915-e0197915
• Main Authors: Sangineto, Moris, Graziano, Giusi, D'Amore, Simona, Salvia, Roberto, Palasciano, Giuseppe, Sabbà, Carlo, Vacca, Michele, Cariello, Marica
• Format: Article
• Language: English
• Subjects: Adult; Analysis; Atrophy; Autoimmune diseases; Biological markers; Biology and Life Sciences; Biomarkers; Biopsy; Blood; Blood cells; Celiac disease; Celiac Disease - diet therapy; Celiac Disease - genetics; Cell proliferation; Cytokines; Diet; Diet, Gluten-Free; DNA microarrays; Family medical history; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene regulation; Genes; Gluten; Gluten-free diet; Haplotypes; Health aspects; Humans; Immunity; Immunoglobulins; Inflammation; Inflammatory response; Interdisciplinary aspects; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Lymphocytes; Male; Medicine; Medicine and Health Sciences; Metabolism; Microarray Analysis; Microbiota; Nutrition research; Patients; Peripheral blood mononuclear cells; Population; Research and Analysis Methods; Rodents; Serology; Signal transduction; Small intestine; Transcriptome - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0197915

Celiac disease (CD) is a systemic disorder characterized by an immune-mediated reaction to gluten and a wide spectrum of clinical manifestations. Currently, the main treatment of CD is represented by adherence to a gluten-free diet (GFD) which determines the resolution of symptoms, and the normalization of the serology and of the duodenal villous atrophy. In the present study, we aimed to identify changes in gene expression in peripheral blood mononuclear cells (PBMCs) of celiac patients on GFD for at least 2 years, in order to identify novel disease biomarkers and candidate targets for putative therapeutic approaches. Microarray analysis was performed on PBMCs from 17 celiac patients on long-term GFD and 20 healthy controls. We identified 517 annotated genes that were significantly modulated between celiac patients and controls. Significant biological pathways were functionally clustered using the Core Function of Ingenuity System Pathway Analysis (IPA). Intriguingly, despite being on a GFD, celiac patients exhibited a peculiar PBMC profile characterized by an aberrant expression of genes involved in the regulation of immunity, inflammatory response, metabolism, and cell proliferation. Random forest algorithm was then used to validate the prediction ability of core genes as classifiers of the "celiac status". In conclusion, our study identified a characteristic PBMCs signature profile in clinically asymptomatic celiac patient.