STRICTuring Crohn’s disease assessment using advanced Ultrasound and magnetic REsonance imaging techniques for evaluation of inflammation and fibrosis (STRICTURE)

Krisztina Gecse © Krisztina Gecse

Aim of research

Patients with Crohn’s Disease present predominantly with inflammation; however, a significant proportion of patients already exhibit strictures at diagnosis or develop fibrostenotic complications during their disease course. Whereas predominantly inflammatory strictures are likely to benefit from medical therapy, predominantly fibrotic strictures often require a surgical approach. As strictures are rarely identified merely as fibrotic or inflammatory, identifying the predominant component of the stricture is necessary to guide clinical decision making. However, currently used imaging modalities are unable to adequately determine stricture composition.

Intestinal ultrasound (IUS) and MRI are both frequently used in the evaluation of disease activity in CD. Previous studies have shown that advanced modalities of both techniques are promising for the characterisation of stricture composition. However, data are scarce and most studies have not combined MRI and IUS parameters.

Therefore, the aim of the STRICTURE study is to evaluate the use of state-of-the-art cross-sectional imaging parameters to identify stricture composition, as defined by the histopathological degree of inflammation and fibrosis in the surgical resection specimen.

Role of PADI4 in Crohn's disease: the citrullination of proteins in the transition from inflammation to fibrosis

Gabriele Dragoni © Gabriele Dragoni

Aim of research

Citrullination is a post-translational modification of proteins, mediated by enzymes called PADs (peptidylarginine deiminases). PAD4 has recently been shown to citrullinate histone 3 (H3cit) in the nucleus, leading to the expulsion of extracellular traps from neutrophils (NETs), whose presence in Crohn’s Disease (CD) is debated.

The aim of this project is to investigate the role of PAD4 in inflammatory and fibrotic contexts of ileal CD.

Understanding the mechanisms of anti-TNF treatment failure in patients with Crohn’s Disease: a proteomic analysis of the PANTS cohort

Neil Chanchlani © Neil Chanchlani

Aim of research

In the Personalised Anti-TNF Therapy in Crohn’s Disease (PANTS) prospective cohort study, we followed 1,610 patients with Crohn’s Disease treated with infliximab or adalimumab for three years. About one in four patients experienced primary non-response and one-third of initial responders lost response, leaving only one-third in remission at one year.  

A limited number of proteomic markers have been implicated in anti-TNF treatment failure, but their relative effects and interactions have not been fully explored. We aim:

1. To identify novel protein biomarkers linked to intestinal inflammation and immunity that influence pharmacokinetic or pharmacodynamic related primary non-response and non-remission at one year, using two multiplex Olink proteomic panels.
2. Validate previously postulated protein markers associated with anti-TNF primary non-response and non-remission at one year, including TREM-1, oncostatin M, Vitamin D, ASCA, ANCA and anti-OmpC.

CCR6 blockade as novel therapeutic strategy against inflammatory bowel disease

Simona Bertoni © Simona Bertoni

Aim of research

CCL20 and its cognate receptor CCR6 are dysregulated in the colonic mucosa and serum of IBD patients; their genes have been identified as susceptibility genes for IBD and an anti-CCL20 neutralizing antibody has been reported to be beneficial in TNBS-induced colitis.
Our working hypothesis is that blocking the CCL20-CCR6 axis represents a novel and promising approach to IBD therapy by limiting neutrophil recruitment to the inflamed tissues and by restoring the balance of effector/regulatory T cells.
Accordingly, our aim is the preclinical validation of small-molecule CCR6 antagonists as potential drug candidates for the treatment of IBD.

Unraveling the immunoregulatory effects of local mesenchymal stromal cell therapy in patients with IBD

Marieke Barnhoorn © Marieke Barnhoorn

Aim of research

Local mesenchymal stromal cell (MSC) therapy is approved for the treatment of Crohn’s Disease-associated perianal fistulas. However, little is known about the mechanism(s) of action of local MSC therapy. In this project we intend to unravel the engraftment and immunoregulatory effects of local MSC therapy in patients with refractory IBD.

Arshdeep Singh © Arshdeep Singh

ECCO-AOCC Travel Grant Awardee

I accepted the ECCO AOCC Travel Grant 2020 with great pleasure and in all humility. The grant enabled me to visit Helsinki University Central Hospital in Finland between January 13 and March 6, 2020. This gave me the opportunity to increase my knowledge on the management of IBD patients and to gain insight into the faecal microbiota transplant and human microbiome research programme in Finland. At the Hospital District of Helsinki and Uusimaa (HUS), I attended the IBD clinics and IBD inpatient rounds, which greatly enriched my experience. Further, I learned more about IBD endoscopy, including double-balloon enteroscopy and capsule endoscopy for Crohn’s Disease and faecal microbiota transplant (FMT). I intend to deploy this knowledge at our IBD centre to foster further professional growth.

Comparative accuracy of the standard Lémann index versus the simplified Lémann index for Crohn’s Disease: a prospective observational cohort study

Ferdinando D'Amico © Ferdinando D'Amico

Aim of research

Crohn's Disease (CD) is an idiopathic Inflammatory Bowel Disease (IBD) characterised by transmural inflammation of the affected tracts. The uncontrolled inflammation can lead to bowel damage, defined as the onset of strictures, abscesses or fistulas negatively impacting patients' quality of life and outcomes. The Lémann index (LI) is a recently validated tool that was specifically designed to assess the presence of penetrating or stenosing lesions and to quantify their severity. LI is a complex and time-consuming score which is based on imaging [magnetic resonance imaging (MRI)] and endoscopic procedures. Of note, it is mainly used in clinical trials, while its use in clinical practice is limited. Our aim was to develop a simplified LI and to compare the correlation between this simplified LI and the standard LI in assessing bowel damage.

Targeting CD4+ T-cell plasticity in Inflammatory Bowel Diseases

Andres Machicote © Andres Machicote

Aim of research

Inflammatory Bowel Diseases (IBD) are devastating diseases induced by a breakdown of gut homeostasis, in which CD4⁺ effector T cells are major mediators of the inflammatory response. Interestingly, CD4⁺ effector T cells can convert into regulatory T cells, thereby controlling inflammation. However, the forces driving this T-cell plasticity remain largely unexplored, especially in IBD patients. In this regard, changes in the microbiota that can induce different T-cell profiles are commonly observed during IBD. The present proposal aims to elucidate how CD4⁺ T-cell plasticity can be modulated from a pro-inflammatory towards an anti-inflammatory profile in IBD patients. Our hypothesis is that the microbiota may modulate T cells towards an anti- or pro-inflammatory profile. To address this issue, we aim to analyse T-cell plasticity in IBD patients and mouse IBD models, and to correlate our findings with the microbiota composition. Furthermore, we will study whether antibiotics commonly used to treat IBD affect T-cell plasticity through microbiota-dependent processes.

Michael Scharl © ECCO

Marc Ferrante © ECCO

Sebastian Zeissig © ECCO

Similarities and differences in the pathogenesis of immune-mediated inflammatory disorders 

This year’s SciCom Workshop focussed on common and distinct pathways in immune-mediated disorders and the application of this knowledge for early disease recognition and interception as well as for the treatment of established disease.

Sebastian Zeissig  © ECCO

During the ECCO’20 Vienna Congress, the Scientific Committee cordially welcomed Konstantinos Papamichail and Yves Panis as new members of SciCom.

Konstantinos Papamichail has been an ECCO Member since 2007 and has participated in several ECCO Activities, including the 7th ECCO Advanced Course and the ECCO ‘EXIT strategies’ Topical Review. He is a reviewer of the ECCO Grants and also a member of the editorial board of JCC. After completing his PhD in Pharmacology and his GI Fellowship in Greece, Kostas joined the Leuven IBD group as a post-doctoral researcher for 3 years and was also a recipient of an ECCO Fellowship. For the last 5 years he has been working at the Beth Israel Deaconess Medical Center in Boston, where his research has focussed on the role of therapeutic drug monitoring of biologics in IBD. He is the author of numerous publications and his goal is to stimulate scientific interactions in the ECCO Community and beyond and to interact with the other ECCO Committees in order to promote and support national and international IBD research efforts towards the better care of patients with IBD.