Disease-specific regulation of gene expression in a comparative analysis of juvenile idiopathic arthritis and inflammatory bowel disease

Objective.With the increasing use of etanercept for juvenile idiopathic arthritis (JIA) new possible adverse events are reported including new autoimmune diseases. Our purpose was to examine if the incidence of inflammatory bowel disease (IBD) in patients with JIA using etanercept is higher than in the healthy age-matched population. We give the clinical characteristics of the IBD in patients with JIA using etanercept.Methods.The national JIA registries for etanercept of The Netherlands, Germany, Finland, Denmark, and Italy were searched for patients with JIA and IBD. The total number of patient-years was used to calculate incidence. The physicians of the identified patients were asked to give clinical details.Results.Thirteen cases of IBD in JIA patients were identified in the registries between 1999 and 2008. The IBD incidence in JIA patients while using etanercept was 362 per 100,000 patient-years under etanercept, about 43 times higher than in the general pediatric population. Clinical presentation of IBD in JIA patients using etanercept was similar to that in non-JIA patients. The median time between onset of JIA and onset of IBD was 6 years and 10 months. The time between the start of etanercept and the first appearance of IBD symptoms was between 9 days and 4.5 years.Conclusion.The incidence of IBD in JIA patients using etanercept seems to be markedly increased, analyzing data from European registries. This incidence of IBD in the etanercept registries cannot be compared to the incidence of IBD in JIA patients using other treatment without etanercept, because such registries do not exist yet in all European countries. These findings are in keeping with a report of 8 new IBD cases occurring in French children with JIA using etanercept. These findings illustrate the need for large international disease-specific registries focused on outcome and pharmacovigilance.

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Comparative analysis of colonic gene expression of three experimental colitis models mimicking inflammatory bowel disease

Inflammatory Bowel Diseases ◽

10.1002/ibd.20079 ◽

2007 ◽

Vol 13 (3) ◽

pp. 325-330 ◽

Cited By ~ 104

Author(s):

Anje A. te Velde ◽

Floor de Kort ◽

Ellen Sterrenburg ◽

Inge Pronk ◽

Fiebo J.W. ten Kate ◽

...

Keyword(s):

Gene Expression ◽

Inflammatory Bowel Disease ◽

Comparative Analysis ◽

Bowel Disease ◽

Experimental Colitis ◽

Inflammatory Bowel

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37 Monitoring the evolution of inflammatory bowel disease (IBD) in pediatric and adult cohorts of patients to identify biomarkers to predict cancer risk

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0037 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A38-A38

Author(s):

Shilpa Ravindran ◽

Heba Sidahmed ◽

Harshitha Manjunath ◽

Rebecca Mathew ◽

Tanwir Habib ◽

...

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Colorectal Cancer ◽

Inflammatory Bowel Disease ◽

Bowel Disease ◽

Mesenchymal Transition ◽

Increased Risk ◽

Hamad Medical Corporation ◽

Inflammatory Bowel ◽

Left And Right

BackgroundPatients with inflammatory bowel disease (IBD) have increased risk of developing colorectal cancer (CRC), depending on the duration and severity of the disease. The evolutionary process in IBD is driven by chronic inflammation leading to epithelial-to-mesenchymal transition (EMT) events in colonic fibrotic areas. EMT plays a determinant role in tumor formation and progression, through the acquisition of ‘stemness’ properties and the generation of neoplastic cells. The aim of this study is to monitor EMT/cancer initiating tracts in IBD in association with the deep characterization of inflammation in order to assess the mechanisms of IBD severity and progression towards malignancy.Methods10 pediatric and 20 adult IBD patients, admitted at Sidra Medicine (SM) and Hamad Medical Corporation (HMC) respectively, have been enrolled in this study, from whom gut tissue biopsies (from both left and right side) were collected. Retrospectively collected tissues (N=10) from patients with malignancy and history of IBD were included in the study. DNA and RNA were extracted from fresh small size (2–4 mm in diameter) gut tissues using the BioMasher II (Kimble) and All Prep DNA/RNA kits (Qiagen). MicroRNA (miRNA; N=700) and gene expression (N=800) profiling have been performed (cCounter platform; Nanostring) as well as the methylation profiling microarray (Infinium Methylation Epic Bead Chip kit, Illumina) to interrogate up to 850,000 methylation sites across the genome.ResultsDifferential miRNA profile (N=27 miRNA; p<0.05) was found by the comparison of tissues from pediatric and adult patients. These miRNAs regulate: i. oxidative stress damage (e.g., miR 99b), ii. hypoxia induced autophagy; iii. genes associated with the susceptibility to IBD (ATG16L1, NOD2, IRGM), iv. immune responses, such as TH17 T cell subset (miR 29). N=6 miRNAs (miR135b, 10a196b, 125b, let7c, 375) linked with the regulation of Wnt/b-catenin, EM-transaction, autophagy, oxidative stress and play role also in cell proliferation and mobilization and colorectal cancer development were differentially expressed (p<0.05) in tissues from left and right sides of gut. Gene expression signature, including genes associated with inflammation, stemness and fibrosis, has also been performed for the IBD tissues mentioned above. Methylation sites at single nucleotide resolution have been analyzed.ConclusionsAlthough the results warrant further investigation, differential genomic profiling suggestive of altered pathways involved in oxidative stress, EMT, and of the possible stemness signature was found. The integration of data from multiple platforms will provide insights of the overall molecular determinants in IBD patients along with the evolution of the disease.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

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Disease-Related Knowledge in New Zealand Children with Inflammatory Bowel Disease (IBD) and Their Parents

Gastrointestinal Disorders ◽

10.3390/gidisord3010002 ◽

2021 ◽

Vol 3 (1) ◽

pp. 23-28

Author(s):

Laura Appleton ◽

Andrew S. Day

Keyword(s):

Inflammatory Bowel Disease ◽

New Zealand ◽

Bowel Disease ◽

Patient Adherence ◽

Intervention Strategy ◽

Specific Knowledge ◽

Poor Knowledge ◽

Clinical Consequences ◽

Inflammatory Bowel ◽

Disease Specific

Insufficient disease-related knowledge can be a barrier to the effective management of the unpredictable and lifelong course of inflammatory bowel disease (IBD). Patients with chronic illnesses have high non-adherence rates, with direct clinical consequences. While no single intervention strategy can improve the adherence of all patients, the success of attempts to improve patient adherence depends upon the realistic assessment of patients’ knowledge and their understanding of the regimen. The aim of this study was to assess the disease-specific knowledge of the parents and patients with IBD in the South Island of New Zealand, and identify areas of poor knowledge. Families of children diagnosed with IBD were asked to complete the IBD Knowledge Inventory Device (IBD-KID). Patients 10 years and older were asked to participate along with their parents. Of 110 families, 91 responded, with completed questionnaires received from 153 parents and 66 patients. Overall, parents scored significantly higher (13.64 ± 3.88) than their children (10.03 ± 4.07; p < 0.001). Areas of poor knowledge included aspects of treatment (both conventional and alternative), along with long-term disease outcomes. This study has shown clear areas of concern in this population’s disease-specific knowledge of their disease. This should be addressed through targeted education for both the patient and the parents to improve not only their knowledge, but also their adherence and disease self-management.

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