SciCom
17December2019

ECCO Grant Study Synopsis: Nik Ding

Nik Ding, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Volume 14, Issue 4

17December2019

ECCO Grant Study Synopsis: Petra Bacher

Petra Bacher, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 14, Issue 4

17December2019

ECCO Grant Study Synopsis: Lissy de Ridder

Lissy de Ridder, ECCO Grant Awardee

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.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 14, Issue 4

11October2019

ECCO Fellowship Study Synopsis: Ramona Bruckner

Ramona Bruckner, ECCO'19 Fellowship Awardee

The role of fibroblasts in the pathogenesis of Crohn’s Disease-associated fistulas and in mesenchymal stem cell therapy  

 


Ramona Bruckner
© 
Ramona Bruckner

Aim of the research

Perianal fistulas are a severe and frequent complication in Crohn’s Disease (CD) patients, significantly affecting their quality of life. High recurrence rates, incomplete fistula healing and non-responding patients make the treatment challenging. Despite some novel insights, current knowledge about the pathogenesis of fistula formation is still limited. Fibroblasts are abundantly present in fistulas and were recently reported to regulate Th1 cell activity in Inflammatory Bowel Disease (IBD). Our hypothesis is that fibroblasts act as the key drivers of this disease complication by regulating inflammatory cell recruitment. We will investigate which pro-inflammatory cytokines and chemoattractants are produced by fistula-derived fibroblasts and how they influence recruitment of immune cells, leading to sustained inflammation. Our second hypothesis is that mesenchymal stem cells (MSCs) can normalise this fibroblast-driven pro-inflammatory environment.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 14, Issue 3

11October2019

ECCO Fellowship Study Synopsis: Javier Conde Aranda

Javier Conde Aranda, ECCO'19 Fellowship Awardee

PTPN2 and TiO2 in the pathogenesis of Inflammatory Bowel Disease  

 

conde arandaJavier Conde Aranda
© 
Javier Conde Aranda

Aim of the research

Titanium dioxide (TiO2) may play a pivotal role in the onset and perpetuation of chronic intestinal inflammation. These effects may be genetically triggered, and variations in IBD risk genes, such as PTPN2, may contribute critically to the detrimental effect of TiO2 in vivo. For these reasons, we will study the combined effects of the presence of disease-associated genetic PTPN2 variations and TiO2 microparticles on the development of chronic intestinal inflammation and on inflammasome activity, as well as the subsequent consequences for the host immune system, in particular innate immune responses. The study will demonstrate the relevance of TiO2 in the pathogenesis of intestinal inflammation in vivo. To address the aforementioned aims, we will:

1. Analyse whether PTPN2-mediated inflammasome activation can control TiO2-induced intestinal inflammation.
2. Demonstrate whether the presence of the disease-associated PTPN2 variant affects NLRP3 inflammasome activation and intestinal inflammatory responses to TiO2 in IBD patients.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 14, Issue 3

12June2019

New SciCom Members

Janneke van der Woude, SciCom Chair

Janneke van der Woude2Janneke van der Woude
© ECCO

During the ECCO’19 Copenhagen Congress the Scientific Committee cordially welcomed Marc Ferrante as a new member.

Marc Ferrante has been an individual member of ECCO since 2008 and has contributed to several ECCO Activities and Initiatives. He was one of the Y-ECCO Founders and Y-ECCO Chairs. His career in ECCO continued in 2015 with a position on ClinCom, and he subsequently became chair of this committee in 2017. 

 

Posted in ECCO News, SciCom, Committee News, Volume 14, Issue 2

30April2019

Report on the 7th SciCom Workshop at ECCO'19

Sebastian Zeissig, SciCom Member

Sebastian Zeissig2Sebastian Zeissig
© ECCO

Mechanisms and therapeutic modulation of mucosal healing in IBD 

We saw one of the best-ever attended SciCom Workshops this year, with exciting talks and highly interactive discussions around the topic of mucosal healing in IBD. In two sessions, the mechanisms of intestinal regeneration and its disruption in IBD and novel approaches to the clinical assessment and therapeutic modulation of mucosal healing were discussed.

 

Posted in ECCO News, SciCom, Committee News, Congress News, ECCO'19, Volume 14, Issue 1

30April2019

ECCO Fellowships and Grants Report

Janneke van der Woude, SciCom Chair

Janneke van der Woude1Janneke van der Woude
© ECCO

One of the main goals of ECCO is to promote IBD-related basic and clinical research as well as to foster interaction and productive collaboration among European research groups working in the IBD field.

To achieve this goal, ECCO continues to award Grants, Fellowships and Travel Awards, and the number of awardees has now increased to an amazing total of more than 25.  

Posted in ECCO News, SciCom, Committee News, Volume 14, Issue 1

11December2018

ECCO Grant Study Synopsis: Federica Ungaro

Federica Ungaro, ECCO Grant Winner

Definition of IBD-associated gut virome via next-generation sequencing: Novel insights for disease onset and treatments

 

Federica UngaroFederica Ungaro
© Federica Ungaro

Aim of Research

Viral infections have been reported to be the primary trigger in many diseases. Preliminary results from RNA-seq analysis performed on mucosal biopsies of patients with active Crohn’s Disease (CD) or Ulcerative Colitis (UC) and healthy controls revealed indicated an IBD-specific viral signature, characterised by increased levels of viral RNAs, especially in patients with UC.

Although analyses on gut virome composition are available, to date nobody has described which viruses are involved in IBD onset. We propose characterising the viral composition of gut mucosal samples from early-diagnosed patients with IBD and healthy subjects by exploiting transcriptomic analysis. Moreover, through RNA silencing experiments, we will investigate whether the inhibition of viral-specific RNAs may be beneficial in mucosal biopsies from patients with active IBD. Results obtained from this study are expected to lead to the unveiling of a novel concept depicting IBD aetiopathogenesis as related to specific viral infections. This will arguably offer new therapeutic insights and promote the search for antiviral drugs for the treatment of IBD.

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 4

11December2018

ECCO Grant Study Synopsis: Dina Danso-Abeam

Dina Danso-Abeam, ECCO Grant Winner

Identification of the functional role of NLRP6 in human Crohn’s Disease

 

03 SciCom 8 8 Danso Abeam Dina MASTER ECCO Grant synopsis rounded Dina Danso-Abeam
© Dina Danso-Abeam

Aim of Research

The introduction of biological therapies such as anti-TNF has led to a decrease in surgery in IBD. However, many patients do not benefit from this treatment: One-third of patients do not respond to induction therapy (primary non-responders) and about half of primary responders lose response over time (secondary non-responders). This is in part due to therapeutic targeting of generalised inflammation rather than specific targeting of well-defined molecular mediators of IBD pathogenesis.

Most recently, the nod-like receptor NLRP6 has come to light for its potential role in local inflammation driven by gut microbial dysbiosis, albeit almost all data are emerging from mouse models. Our preliminary data from a patient harbouring a novel NLRP6 mutation show significant dysregulation in multiple immune cells, providing strong evidence for the role of NLRP6 in immune homeostasis. Taking into account the high expression of NLRP6 in human intestine, this project aims to decipher the role of NLRP6 in the pathology of Crohn’s Disease (CD).

Posted in ECCO News, SciCom, Committee News, Fellowships & Grants Synopsis Reports, Volume 13, Issue 4