An integrative analysis of DNA methylation and RNA-Seq data in human adipose stem cells of Crohn’s Disease patients with different clinical activity

Carolina Serena © Carolina Serena

Aim of Research

1. To identify an epigenetic signature in human adipose stem cells (hASCs) isolated from CD patients with different clinical activity, and to compare this signature with that of hASCs from healthy donors (study of epigenetics).
2. To explore the effects of DNA methylation on the regulation of gene expression in hASCs isolated from the same cohort (study of transcriptomics).
3. Integration of data to identify the interplay between differentially methylated DNA sites and the transcriptome profile of hASCs from healthy and CD subjects that could be involved in the dysregulation of hASCs associated with CD.

Sarcopenia as a Predictor of Anti-TNF Non-Response in Crohn’s Disease

Nik Ding © Nik Ding

Aim of Research

• To demonstrate that sarcopenia, myopenia and body composition parameters are associated with lower anti-TNF drug levels and primary non-response in patients with moderate to severe Crohn’s Disease who are anti-TNF naive.
• To demonstrate that sarcopenia is a biomarker of primary non-response (PNR) and secondary loss of response (SLR) to anti-TNF therapy.
• To demonstrate that sarcopenia/myopenia is a biomarker of primary non-response (PNR) to anti-TNF therapy due to inadequate anti-TNF dosing by use of therapeutic drug monitoring.
• To demonstrate that improvement of sarcopenia/myopenia increases anti-TNF drug levels and clinical response to anti-TNF drugs.

The hypothesis is that sarcopenia is predictive of low anti-TNF drug levels and possible primary non-response to anti-TNF therapy, and, in addition, that sarcopenia is a predictor for primary non-response and loss of response to anti-TNF therapy which correlates with anti-TNF levels at weeks 4 and 12.

The immune repertoire of microbe-reactive T cells in blood and tissue of IBD patients

Petra Bacher © Petra Bacher

Aim of Research

Dysregulated T cell reactions against intestinal antigens are considered to be a causal or driving factor for Inflammatory Bowel Diseases (IBD). So far, technical limitations concerning the detection and characterisation of microbiota-reactive T cells have prevented determination of the exact contribution of specific T cell subsets against individual microbes to the intestinal balance and its dysregulation in IBD. Analysing the phenotype, function and T cell receptor (TCR) repertoire of microbe-specific T cells in blood and intestinal mucosa of IBD patients will therefore provide important insights to fundamental questions on the clonal expansion of pro- and anti-inflammatory microbe-reactive T cells, their clonal relation and stability and the sites (blood and/ or intestinal tissue) at which the relevant T cell subsets are located.

Infliximab in Paediatric Crohn’s Disease; in whom to start (ImProve)

Lissy de Ridder © Lissy de Ridder

Aim of Research

Crohn’s Disease (CD) is a heterogeneous chronic immune-mediated inflammatory disease. To improve management, precision medicine is urgently needed to target the underlying pathogenic immune response that is driving disease. There is a key unmet need to identify biomarkers that will predict the need for, and the response to, anti-tumor necrosis factor (TNF) treatment, including in paediatric CD. This constitutes the aim of the present project. The use of such predictive biomarkers will help to avoid delay in effective treatment, complications due to ongoing inflammation and exposure of non-responders to anti-TNF. We hypothesise that genetic expression profiling, in combination with thorough patient characterisation, will lead to such biomarkers and thereby improve targeted anti-TNF use in paediatric CD.

Nuha Yassin © ECCO

Dear IBD Friends,

Warm greetings to you all at the start of the festive season. As we prepare to welcome the New Year, we are also preparing to welcome you back to our IBD and ECCO hub in the beautiful city of Vienna. Our introduction to ECCO'20 starts slightly differently this time, with a short prelude about IBD standards.

Charlotte Hedin © ECCO

Professor Fiona Powrie is the Director of the Kennedy Institute of Rheumatology at the University of Oxford. Her work has been seminal in defining the mechanisms that govern and regulate immune responses in the gut. Her research has revealed the pivotal role of regulatory T cells, interleukin-10, interleukin-23 and transforming growth factor-β (TGF-β) in intestinal inflammation.

No association between pseudopolyps and colorectal neoplasia in patients with inflammatory bowel diseases

Mahmoud R, Shah SC, Ten Hove JR, Torres J, Mooiweer E, Castaneda D, Glass J, Elman J, Kumar A, Axelrad J, Ullman T, Colombel JF, Oldenburg B, Itzkowitz SH; Dutch Initiative on Crohn and Colitis

Gastroenterology. 2019;156:1333–44.e3.

Introduction

Sailish Honap © Sailish Honap

Patients with Inflammatory Bowel Disease (IBD) are at an increased risk of developing high-grade dysplasia and colorectal carcinoma [1, 2]. The risk of carcinogenesis, driven by chronic inflammation, increases with several factors, including duration and anatomic extent of colitis, family history and the presence of primary sclerosing cholangitis (PSC). European clinical guidelines for colonoscopy surveillance in this high-risk cancer population also suggest a shorter surveillance interval for those with post-inflammatory polyps (PIPs), also known as pseudopolyps [3–5]. PIPs are a common finding, more so in Ulcerative Colitis (UC) than in Crohn’s Disease, and are formed after alternating cycles of inflammation and regeneration of the epithelial mucosa. However, data are conflicting and evidence is lacking in this field as previous case control studies have reported up to a 2.5-fold increased risk [6, 7] whereas a more recent cohort study showed no significant association between PIPs and colorectal neoplasia (CRN) [8]. The authors of this study aimed to use a large cohort study to further define the risk of CRN and PIPs in patients with Inflammatory Bowel Disease.  

Crohn’s Disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial

Levine A, Wine E, Assa A, Boneh RS, Shaoul R, Kori M, Cohen S, Peleg S, Shamaly H, On A, Millman P, Abramas L, Ziv-Baran T, Grant S, Abitbol G, Dunn KA, Bielawski JP, Van Limbergen J

Gastroenterology. 2019;157:440–50.

Introduction

Paul Harrow © Paul Harrow

Exclusive enteral nutrition (EEN) is a safe and effective induction treatment for Crohn’s Disease (CD). It is recommended as first-line induction therapy in children and adolescents [1]. However, enteral nutrition is less well tolerated than other options like corticosteroids. A recent meta-analysis found three times as many patients withdrew from enteral nutrition therapy compared to corticosteroids even in the supported setting of clinical trials [2]. There is a clear need for a more acceptable dietary intervention. However, our understanding of the role of diet in CD is incomplete and to date specific diets have not been proven to induce remission. 

Ustekinumab exposure-outcome analysis in Crohn’s Disease only in part explains limited endoscopic remission rates

Verstockt B, Dreesen E, Noman M, Outtier A, Van den Berghe N, Aerden I, Compernolle G, Van Assche G, Gils A, Vermeire S, Ferrante M

J Crohns Colitis. 2019;13:864–72.

Introduction

Samantha Campbell © Samantha Campbell

Ustekinumab is licenced to treat moderate-severe Crohn’s Disease (CD) [1]. Ustekinumab induction is administered via intravenous (IV) infusion at a dose of 6 mg/kg at week 0, followed by a subcutaneous (SC) maintenance injection of 90 mg at week 8.

The UNITI programme demonstrated that ustekinumab can induce and maintain clinical remission. However, there is a paucity of real-life data in patients with CD receiving the mentioned IV induction and SC maintenance dosing of ustekinumab. Real-life data on therapeutic drug monitoring and biomarkers, such as faecal calprotectin, remain a relatively unexplored area with ustekinumab, with discrepancies in the literature [2, 3]. . 

Dominik Bettenworth © ECCO

Dear Y-ECCO Friends,

I hope you all are doing well.

During my summer leave, I read a book on the time horizon principle. The author supposes that the productivity of the most successful people on the planet results from the balance between three core components: Time for yourself, relationships and work. As you all, hopefully, have had sufficient time for yourself and your family during your holidays, here are some ways to expand your (professional) relationships and work skills: