Multiplex gene expression profile in inflamed mucosa of patients with Crohn’s disease ileal localization: A pilot study  

作　　者：Francesco Giudici Letizia Lombardelli Edda Russo Tiziana Cavalli Daniela Zambonin Federica Logiodice Ornela Kullolli Lamberto Giusti Tatiana Bargellini Marilena Fazi Livia Biancone Stefano Scaringi Ann Maria Clemente Eloisa Perissi Giovanni Delfino Maria G Torcia Ferdinando Ficari Francesco Tonelli Marie-Pierre Piccinni Cecilia Malentacchi 

机构地区：[1]Department of Experimental and Clinical Medicine,University of Firenze,Firenze 50134,Italy [2]Dipartimento Chirurgico Ortopedico,Ospedale Carlo Poma di Mantova,Firenze 50134,Italy [3]Department of Experimental and Clinical Biomedical Sciences “Mario Serio”,University of Firenze,Firenze 50134,Italy [4]Surgical Unit,Department of Surgery and Translational Medicine,University of Firenze,Firenze 50134,Italy [5]Department of Internal Medicine,University of Roma Tor Vergata,Roma 00133,Italy

出　　处：《World Journal of Clinical Cases》2019年第17期2463-2476,共14页世界临床病例杂志

基　　金：Supported by MIUR-Ministry of Education,University and Research,No.2008X8NRH4_003;Fondazione Cassa di Risparmio di Firenze,No.2008.1581,2009.1301

摘　　要：BACKGROUND Crohn’s disease (CD) is a complex disorder resulting from the interaction of genetic,environmental,and microbial factors.The pathogenic process may potentially affect any segment of the gastrointestinal tract,but a selective location in the terminal ileum was reported in 50% of patients.AIM To characterize clinical sub-phenotypes (colonic and/or ileal) within the same disease,in order to identify new therapeutic targets.METHODS 14 consecutive patients undergoing surgery for ileal CD were recruited for this study.Peripheral blood samples from each patient were collected and the main polymorphisms of the gene Card15/Nod2 (R702W,G908R,and 1007fs) were analyzed in each sample.In addition,tissue samples were taken from both the tract affected by CD and from the apparently healthy and disease-free margins (internal controls).We used a multiplex gene assay in specimens obtained from patients with ileal localization of CD to evaluate the simultaneous expression of 24 genes involved in the pathogenesis of the disease.We also processed surgery gut samples with routine light microscopy (LM) and transmission electron microscopy (TEM) techniques to evaluate their structural and ultrastructural features.RESULTS We found a significant increase of Th17 (IL17A and IL17F,IL 23R and CCR6) and Th1 (IFN-γ) gene expression in inflamed mucosa compared to non-inflamed sites of 14 CD patients.DEFB4 and HAMP,two genes coding for antimicrobial peptides,were also strongly activated in inflamed ileal mucosa,suggesting the overwhelming stimulation of epithelial cells by commensal microbiota.IFN-γ and CCR6 were more expressed in inflamed mucosa of CD patients with ileal localization compared with patients with colonic localization suggesting a more aggressive inflammation process in this site.Morphological analysis of the epithelial lining of Lieberkün crypts disclosed enhanced release activity from goblet mucocytes,whereas the lamina propria contained numerous cells pertaining to various lines.CONCLUSION We observed that the eBACKGROUND Crohn’s disease(CD) is a complex disorder resulting from the interaction of genetic, environmental, and microbial factors. The pathogenic process may potentially affect any segment of the gastrointestinal tract, but a selective location in the terminal ileum was reported in 50% of patients.AIM To characterize clinical sub-phenotypes(colonic and/or ileal) within the same disease, in order to identify new therapeutic targets.METHODS14 consecutive patients undergoing surgery for ileal CD were recruited for this study. Peripheral blood samples from each patient were collected and the main polymorphisms of the gene Card15/Nod2(R702 W, G908 R, and 1007 fs) were analyzed in each sample. In addition, tissue samples were taken from both the tract affected by CD and from the apparently healthy and disease-free margins(internal controls). We used a multiplex gene assay in specimens obtained from patients with ileal localization of CD to evaluate the simultaneous expression of24 genes involved in the pathogenesis of the disease. We also processed surgery gut samples with routine light microscopy(LM) and transmission electron microscopy(TEM) techniques to evaluate their structural and ultrastructural features.RESULTS We found a significant increase of Th17(IL17 A and IL17 F, IL 23 R and CCR6) and Th1(IFN-γ) gene expression in inflamed mucosa compared to non-inflamed sites of 14 CD patients. DEFB4 and HAMP, two genes coding for antimicrobial peptides, were also strongly activated in inflamed ileal mucosa, suggesting the overwhelming stimulation of epithelial cells by commensal microbiota. IFN-γand CCR6 were more expressed in inflamed mucosa of CD patients with ileal localization compared with patients with colonic localization suggesting a more aggressive inflammation process in this site. Morphological analysis of the epithelial lining of Lieberkün crypts disclosed enhanced release activity from goblet mucocytes, whereas the lamina propria contained numerous cells pertaining to various lines.CONCLUSION We obse

关 键 词：Crohn's disease ILEUM Colon Messenger ribonucleic acid Th1/Th17 MICROBIOTA Inflammation 

分 类 号：R[医药卫生]