Inflammatory gene expression profiles in Crohn's disease and ulcerative colitis: a comparative analysis using a reverse transcriptase multiplex ligation-dependent probe amplification protocol.

Abstract

BACKGROUND AND AIMS:

Cytokines and their receptors play a critical role in the pathogenesis of the inflammatory bowel disease (IBD). The aim of this study was to investigate the expression profiles of inflammatory genes in inflamed and non-inflamed colonic tissue samples in patients with Crohn's disease (CD) and ulcerative colitis (UC), and to identify molecular signatures for different IBD phenotypes.

METHODS:

Seventy-one patients diagnosed with IBD (38 CD, 33 UC) and 15 non-IBD controls have been included in the study. For each patient, biopsy samples were obtained during colonoscopy from inflamed (L) and healthy (N) mucosa. We investigated by commercially available reverse-transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) kit the mRNA expression of a set of 40 genes involved in inflammation: cytokines, chemokines, receptors, signal transduction molecules and transcription factors.

RESULTS:

In L biopsies from patients with CD, higher expression levels were found for IL-4 (p=0.009) and IL-12p35 (p=0.0005), whereas in L biopsy samples from patients with UC higher expression levels were found for IL-8 (p=0.03), chemokines SCYA3 (p=0.05), SCYA4 (p=0.01) and glutathione S-transferase P1 (p=0.01). In N biopsies of patients with CD higher expression levels were found for IL-1R (p=0.01) and IL-12p35 (p=0.007), whereas in N biopsies of patients with UC higher expression levels were found for IL-15 (p=0.009) and SCYA8 (p=0.001). The logistic regression analysis has indicated that low expression levels of IL-2 and IL-10, together with higher ASCA IgG titers were independently associated with penetrating/stricturing CD.

CONCLUSIONS:

RT-MLPA is a sensitive and effective method for the evaluation of the profiles of inflammatory genes in IBD, with potential future applications for diagnosis, phenotypic stratification and targeted therapy.

• Authors: Serban Gologan, Razvan Iacob, Daniela Iancu, Speranta Iacob, Bogdan Cotruta, Roxana Vadan, Ana-Maria Catuneanu, Ileana Constantinescu, Ligia Barbarii, Cristian Gheorghe, Mircea Diculescu
• Journal: Journal of Crohn's & colitis (J Crohns Colitis) Vol. 7 Issue 8 Pg. 622-30 (Sep 2013) ISSN: 1876-4479 [Electronic] England
• PMID: 23014361 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Chemical References

• Chemokines
• Cytokines
• RNA, Messenger
• Transcription Factors

Topics

• Adult
• Case-Control Studies
• Chemokines (genetics)
• Colitis, Ulcerative (genetics)
• Crohn Disease (genetics)
• Cytokines (genetics)
• Female
• Gene Expression
• Gene Expression Profiling
• Genotype
• Humans
• Male
• Middle Aged
• Multiplex Polymerase Chain Reaction
• Phenotype
• RNA, Messenger (analysis)
• Signal Transduction (genetics)
• Transcription Factors (genetics)
• Young Adult