Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Sep 6, 2019; 7(17): 2463-2476
Published online Sep 6, 2019. doi: 10.12998/wjcc.v7.i17.2463
Multiplex gene expression profile in inflamed mucosa of patients with Crohn’s disease ileal localization: A pilot study
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
Francesco Giudici, Letizia Lombardelli, Edda Russo, Daniela Zambonin, Federica Logiodice, Ornela Kullolli, Ann Maria Clemente, Eloisa Perissi, Maria G Torcia, Marie- Pierre Piccinni, Department of Experimental and Clinical Medicine, University of Firenze, Firenze 50134, Italy
Tiziana Cavalli, Dipartimento Chirurgico Ortopedico, Ospedale Carlo Poma di Mantova, Firenze 50134, Italy
Lamberto Giusti, Giovanni Delfino, Cecilia Malentacchi, Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Firenze, Firenze 50134, Italy
Tatiana Bargellini, Marilena Fazi, Stefano Scaringi, Ferdinando Ficari, Francesco Tonelli, Surgical Unit, Department of Surgery and Translational Medicine, University of Firenze, Firenze 50134, Italy
Livia Biancone, Department of Internal Medicine, University of Roma Tor Vergata, Roma 00133, Italy
Author contributions: Giudici F and Lombardelli L equally contributed to this work. Malentacchi C and Piccinni MP conceived the study. Giudici F, Cavalli T, Zambonin D and Bargellini T collected the samples. Lombardelli L, Logiodice F, Kullolli O, Russo E and Giusti L performed the experiments. Lombardelli L and Clemente AM performed the statistical analysis. Torcia MG and Piccinni MP partecipated in the writing of the study protocol and in the revision of the manuscript for important intellectual content with Ficari F, Tonelli F, Biancone L, Fazi M, Scaringi S and Delfino G. Perissi E and Russo E edited the manuscript. Malentacchi C, Giudici F, Russo E, Piccinni MP wrote the manuscript. Malentacchi C and Russo E provided funding acquisition. All authors read, commented, and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by EC of AOUC of Florence on May 2nd, 2011, No. 2011/0018055 rif.95/10, authorization Gen Dir 17/572011 No. 2011/0018055.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Edda Russo, PhD, Academic Research, Postdoctoral Fellow, Biologist, Department of Experimental and Clinical Medicine, University of Firenze, Viale Pieraccini 6, Firenze 50134, Italy.edda.russo@unifi.it
Supported by MIUR-Ministry of Education, University and Research, No. 2008X8NRH4_003; Fondazione Cassa di Risparmio di Firenze, No. 2008.1581, 2009.1301.
Telephone: +39-55-2758330 Fax: +39-55-7947449
Received: March 20, 2019
Peer-review started: March 20, 2019
First decision: May 9, 2019
Revised: July 12, 2019
Accepted: July 27, 2019
Article in press: July 27, 2019
Published online: September 6, 2019
ARTICLE HIGHLIGHTS
Research background

The interplay of environmental, genetic and microbial elements influences the etiopathogenesis of Crohn’s disease (CD). Differences in the clinical course of CD have recently been reported in patients with ileal or colonic localization of the inflammatory process.

Research motivation

Aim of this study was to define biochemical and histological differences in intestinal biopsies from patients with ileal or colonic localization of Crohn disease in order to identify new assays which can be useful for planning individual therapeutic strategies

Research objectives

Main objective of the current research was to investigate the expression of genes involved in immune-inflammatory pathways in gut mucosa from patients with ileal or colonic localization of CD and to correlate the results of gene expression with those obtained through a classical morphological analysis of surgical biopsies.

Research methods

A Multiplex Gene Assay was used to assess the simultaneous expression of 24 genes related to immune-inflammatory process and to CD pathogenesis. Structural and ultrastructural features of gut samples were also evaluated through Light microscopy (LM) and Transmission Electron Microscopy (TEM) techniques.

Research results

We observed a strong activation of genes involved in TH-1- and TH-17 immune response in patients with ileal localization of CD compared to patients with colonic localization. In addition, the expression of genes for antimicrobial peptides as DEFB4 and HAMP was found highly stimulated in ileal mucosa from CD patients suggesting a possible interference with microbial commensals at this site.

Research conclusions

Our results indicate that patients with ileal localization of CD have a stronger activation of TH-1 and TH-17 immune-inflammatory responses compared with patients with colonic localization of the disease thus defining a clear subclinical phenotype of CD.

Research perspectives

These results may suggest that therapeutic strategies with biological drugs in CD patients can be differentiated depending on the location of the disease