. to understand the role of metabolism in IBD
- to identifiy key metabolic principles (SCFA, Bile Acid, Tryptophan)  that have shown to be relevant in the pahtophysiology of IBD
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Educational objectives:
Give an overview of recently published work on IBD / Crohn's disease / ulcerative colitis

Summary
Possible subjects will include:
1) Very early-onset IBD
2) Granulomatous gastritis
3) Appendiceal inflammation in Crohn's disease and in ulcerative colitis
4) An important differential diagnosis of Crohn's disease
5) Precursor lesions of IBD-associated neoplasia and features of Crohn's and colitis-associated bowel cancer
6) Something that may come as a surprise

1. To understand the epidemiology of IBD
2. To understand the impact of the disease on quality of life

1) Highlight differences in disease presenting in adolescence compared to adulthood
2) Discuss the concept of transition vs transfer and the risks
3) Review the options available for transition and tools used to measure progress
4) Discuss guidelines

Educational objectives:
1. To understand the different methods of data collection for different study designs e.g qualitative, quantitative, mixed methods
2. To emphasise the role of different types of data collection methods e.g. interview, observation, survey, etc
3. To empasise practical issues to consider when data collecting 

 In this talk we will discuss simple yet often overlooked pearls and tips to get the most of old-school medications, focusing on thiopurines and 5ASA. We will examine which combination of topical and oral 5ASA is best in each clinical scenario, discuss the role of compliance, how to optimize technical aspects of rectal agents, desensitization and factors not to be overlooked which may contribute to recalcitrant IBD. We will also explore metabolite testing for thiopurines in clinical practice and the evidence backing its use for maintenance monotherapy 

1. To discuss what makes a good research question 
2. To review the process of formulating a research question
3. To understand the researcher factors to be considered when formulating a research question  

The aim of this study was to investigate the effect of various immunosuppressants on the humoral immune responses after vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs).

The Target to B! SARS-CoV-2 study is a multicentre study, taking place in 7 Dutch academic hospitals. Patients with the following IMIDs were recruited: Crohn’s disease (CD), ulcerative colitis (UC), auto-immune hepatitis, rheumatic (e.g. rheumatoid arthritis), neurological (e.g. multiple sclerosis) and dermatological IMIDs (e.g. atopic dermatitis). Patients were recruited based on immunosuppressants (table 1) and previous SARS-CoV-2 infection. The control group consisted of healthy subjects and IMID patients without immunosuppressants. SARS-CoV-2 receptor binding domain (RBD) antibodies were measured 28 days after completed SARS-CoV-2 vaccination. Seroconversion was defined as anti-RBD IgG >4 AU/mL. In this abstract, we focus on therapies relevant for inflammatory bowel diseases (IBD) and present results for these treatments from patients with IBD, but also other IMIDs.

Numbers of recruited patients with each immunosuppressant are shown in table 1. Amongst these patients, 312 patients had CD and 176 UC, the rest was diagnosed with another IMID. Seroconversion was reduced in patients receiving sphingosine 1-phosphate (S1P) modulators (all multiple sclerosis patients) while seroconversion was similar to controls in the other treatment groups. However, use of Anti-tumour necrosis factor (TNF), methotrexate, janus kinase (JAK) inhibitor monotherapy and all combination therapies (except for corticosteroids combined with other immunosuppressants) were associated with reduced Sars-CoV-2 antibody titres. Patients with a previous SARS-CoV-2 infection had higher median antibody titres after second vaccination than those without a previous SARS-CoV-2 infection. The type of IMID did not affect seroconversion rates.

No immunosuppressant, registered for IBD, reduced the rates of seroconversion after vaccination against SARS-CoV-2. Some immunosuppressants were associated with lower antibody titres. However, the clinical relevance of lower antibody titres remains unknown. S1P modulators, had a clear negative impact on the humoral response against SARS-CoV-2 after vaccination. This might be relevant in the future as this therapy is currently being approved for UC. Disease aetiology did not impair immunity against SARS-CoV-2 immunity after vaccination. Disclaimer: Absolute numbers of antibody titres and rates of seroconversion will be reported at the conference and are not reported in this abstract as this might negatively impact the current submission process.

Educational objectives:
To provide insights into the role of telemedicine in remote patient management in IBD
To review the evidence for improved treatment outcomes associated with the use of telemedicine and remote monitoring strategies
Highlight some of the potential limitations and the gaps in evidence that need to be addressed in the future

Educational objectives: 

1. To review the elements needed to deliver best care to patients with inflammatory bowel disease.
2. To review the benefits of live patient interaction in the management of inflammatory bowel disease.
3. To emphasize the future role of hybrid care delivery in inflammatory bowel disease
4. To discuss best practices in care delivery in the virtual/digital age
   
   

In response to the COVID-19 pandemic, many jurisdictions quickly to  virtual care models, defined as any remote, technology-based interaction between a health-care provider and a patient or patient representative. It can be a phone call, videoconference, email exchange or a text. While this tool has been essential in reducing the risk of viral transmission, providing care for patients who need ongoing medical attention may have unintended consequences and if not done properly may lead to poorer health outcomes and this includes in patients with inflammatory bowel disease.

While these tools have advantages for certain patient care needs, including providing necessary virtual pathways to care in remote and Indigenous communities, the pandemic experience has also reinforced the vital importance of hands-on in-person care. There are limits to what can be done virtually and the standard of care is often difficult to meet in a virtual care environment.

There are advantages of virtual care, including improving access to care, especially for patients who cannot easily travel to a clinic; simplifying the coordination of care for; saving patients travel time and the cost of missing work or making caregiving arrangements.  In inflammatory bowel disease, disease monitoring has also been facilitated by the widespread use of apps and fecal calprotectin.  However, given the complexity of patients with inflammatory bowel disease there continues a need to see these patients in person to establish and re-enforce the doctor-patient relationship, ensure proper examination and rule out complications and provide the necessary psychosocial support that virtual care cannot meet.

In the future, lessons learned from the necessity of transitioning to virtual care during the pandemic will certainly find themselves into new hybrid care models which employ a mix of in-person evaluation and efficient, secure and meaningful, and effective virtual care.

Educational Objectives:

1. To review the epidemiology of cancer in IBD
2. To understand the impact of IBD medications on incident and recurrent cancer, as well as impact on active cancer
3. To understand the impact of cancer therapies on IBD outcomes
4. To review therapeutic strategies for IBD in individuals with cancer

Paediatric onset IBD represents approximately 20 to 25% of cases of IBD. Paediatric onset IBD is subclassified based on age, namely paediatric IBD (10-16 yrs), early onset IBD (6-10 yrs) and the very early onset IBD (younger than 6 yrs). The last group comprises two very young age groups, namely neonatal ( < 28 days) and infantile IBD (1 mo-2yrs). The prevalence of very early onset IBD varies between 3-15% of all pediatric IBD. Very early onset IBD is a heterogeneous disease with a clinical presentation different from adult IBD. Morphologically there are different patterns described, of which the active chronic enteritis show some resemblance with the classical IBD.  In time the morphological features may be become more obvious to diagnose IBD. The other forms shows some morphological features suggestive of a monogenic form of very early onset IBD, such as apoptosis.Clinically the disease is characterized by a more aggressive course with increase in severity, frequently resistant to the standard therapy. In these circumstances genetic counselling is necessary to exclude monogenic forms of very early onset IBD. These diseases require a specific treatment in function of the defect either at the level of the intestinal barrier or in the immunesystem, resulting in different types of immune deficiencies .

The characteristic histological features of inflammatory bowel disease are a disturbed crypt architecture, basal plasmacytosis and granulomas. Numerous diseases may clinically as well morphologically mimic IBD. Hence to make a diagnosis of IBD close communication between clinicians and pathologists is essential. Different types of infections are mimickers of IBD, such as Yersinia, Entamoeba histolytica. An important mimicker, which may give rise to a differential diagnostic problem, is tuberculosis. The incidence of tuberculosis is rising due to immigration, immunodeficiencies, the use of immunomodulators, … Distinction between Crohn’s disease and tuberculosis is essential as treatment is totally different. Differentiation is based on its clinical presentation, morphology and may be confirmed by different ancillary techniques. A main feature is the presence of granulomas in the biopsy or the wall of resection specimen. Different diseases, restricted to the gastrointestinal tract or systemic, are associated with granulomas in the intestine. Hence the presence of a granuloma implies an extensive differential diagnosis.   

IBD are chronic, life-long disorders associated with complex medical, surgical and psychosocial issues. Therefore, IBD clinics need to have a multidisciplinary team to discuss and strategize the most challenging cases. This will enhance quality of care and may reduce disease burden and morbidity. In this session, the IBD nurse practitioner, gastroenterologist and colorectal surgeon will discuss two challenging cases where teamwork is essential.

Educational objectives
1. To have an overview of the multidisciplinay team
2. Basics fistulizing Crohn's disease and acute severe ulcerative colitis
3. To understand the multidisciplinary approach

1. To review recent epidemiologic data, highlighting the importance of environmental factors
2. To understand the complexity and multiple factors contributing to IBD pathogenesis
3. To acknowledge how the complexity of IBD may affect treatment effects

T cells, as part of the adaptive immune system, are a significant driver of inflammation in Crohn’s disease (CD), yet specific T-cell targets are largely unknown. Genetic factors contribute to a small portion of CD risk including several HLA alleles, such as DRB1*07:01 and HLA-DRB1*01:03, associated with CD. The involvement of HLAs suggests that studying specific T cells could lead to new insights into CD development and progression. In this study, we use established immunoSEQ^® technology to profile T-cell receptors (TCRs) and identify TCRs associated with CD and CD characteristics.

We analyzed TCRs from blood of 1,738 CD cases and 4,970 healthy controls. TCRs that were statistically enriched in cases, but not healthy controls (p <0.001), were termed Enhanced Sequences (ES) associated with CD. An independent cohort of 434 CD cases was used for validation. We inferred associations between the ES and 145 common HLA alleles using data from a separate, HLA-typed dataset. We defined ES clusters by correlating TCRs with single amino acid substitutions.

We identified 1,121 CD-associated ES in the exploratory cohort. These were also enriched in CD cases in our validation cohort (Fig 1A). Using intestinal tissue samples from a subset of cases, we found that a median of 14% ES from individual cases were shared between blood and tissue samples (Fig. 1B). ES breadth (ES diversity relative to total TCR diversity) was significantly associated with history of CD-related surgery (Fig 1C, p < 1x10^-15), with stricturing or fistulizing phenotypes (Fig 1D, p < 1x10^-5 for B1 versus B2 or B3), and with ileal or ileocolonic location (Fig 1E, p < 1x10^-7 for L2 versus L1 or L3).

We found that 202 ES formed clusters of similar sequences consisting of 2-23 members (Fig. 2A). We confidently (p < 0.0001) associated 398 ES to a specific HLA allele (Fig 2B), including 134 of the ES assigned to clusters (Fig 2A). Some clusters, including the largest, had no members that could be assigned to an HLA allele, raising the possibility that these ES clusters bind non-canonical HLAs.

Our discovery set of public TCRs associated with CD indicates that the immune system of CD patients responds to a consistent set of antigens. Importantly, CD ES were present in both tissue and blood, demonstrating that evaluating TCRs in blood may be a surrogate of TCRs in tissue. The HLA allele associations of these ES potentially point to new risk factors and disease insights, such as the involvement of DP and DQ alleles. The association of ES frequency with CD characteristics strongly suggested that further examination of these TCRs may impact CD patient care and advance understanding of the pathophysiology of the disease.

In Inflammatory Bowel Disease (IBD), intestinal barrier dysfunction and epithelial cell injury are believed to be associated with activation of the immune system to drive disease-associated inflammation, which together constitute key features of active disease. Existing drugs used to treat IBD induce endoscopic remission and improvements in mucosal healing  in only a minor proportion of patients, driving a critical need for therapies which lead directly to mucosal healing. Furthermore, predicting patients who may benefit from therapeutics that address specific mechanisms of mucosal healing may augment response rates.

We screened proteins, identified from a meta-analysis of healthy human microbiome, in cellular assays and animal models related to mucosal injury, with the goal of identifying novel therapeutics that have the potential to directly induce mucosal healing. The proteins identified were further optimized by protein engineering to increase their stability as well as gastro-intestinal (GI) targeting via oral administration. For this, therapeutic proteins were expressed using a probiotic, Lactococcus lactis (L.lactis), engineered to display the recombinant proteins on the cell surface, and evaluated for activity in DSS- and DNBS-induced models of colitis in mice. Mechanism of action studies using computational and laboratory based methods to analyze gene expression and direct molecular interactions with human proteins, enabled the identification of pathways modulated by the candidate molecules. These pathways were further evaluated for their ability to identify biomarkers in specific patients most suitable for treatment in a precision medicine approach.

We have identified a novel, healthy microbiome-derived protein that demonstrated robust activity in human epithelial injury assays in vitro. The protein reduced intestinal injury related pathology in mice when orally administered to target directly the GI tract. SG-5-00455, the product based on an L.lactis strain expressing the candidate therapeutic protein, reduced pathology scores, inflammation and barrier function related LPS-binding protein levels to levels comparable to those obtained glucagon-like peptide 2 (GLP-2), as well as improving dysregulated tissue repair and fibrosis-associated gene expression and proteins levels.  SG-5-0455 treatment did not result in systemic exposure, driving its therapeutic activity in a GI-localized manner by targeting pathways related to tissue injury and fibrinolysis.

SG-5-00455, through its novel mechanism of action and oral delivery to directly target tissue repair pathways in the GI-tract, offers the potential to address a large critical need in IBD.

Tissue-resident memory T cells (Trm) persist in peripheral tissues and contribute to pathogen clearance and inflammation. Trm can re-enter the circulation (ex-Trm) and give rise to new effector and Trm populations. Skin-derived ex-Trm can be identified in human blood based on co-expression of the residency marker CD103 and cutaneous leukocyte antigen (CLA), a skin-tropism marker. The existence of ex-Trm derived from the gut would have implications for inflammatory bowel disease (IBD) and its treatment targeting the recruitment of circulating gut-homing cells.

Peripheral blood and colonic biopsies were taken from healthy volunteers and patients with IBD (Crohn’s disease or ulcerative colitis). PBMCs and cells isolated from biopsies by enzymatic digestion were analysed by multi-colour flow cytometry.

More than 80% of colonic αβT cells were Trm, as defined by CD69 expression, in health and IBD; there was no significant increase in cells with a non-resident phenotype in inflamed tissue. Few CD4+ Trm co-expressed CD103. In contrast, CD8+ Trm comprised CD103+ and CD103- subsets, and CD69+CD103- cells were significantly reduced in IBD. Increased staining for KLRG1 and the cytotoxicity-associated protein perforin, indicated a more effector-like Trm phenotype in IBD. Putative gut-derived ex-Trm were identified amongst TCRαβ+CD45RA- blood cells as a β7++CD103+ population, indicative of cells expressing both α4β7 and CD103(α_E)β7 integrin complexes.  A separate CD103β7+α4β7 population defined by 1:1 expression of CD103 and β7 contained CLA+ skin ex-Trm. Gut ex-Trm comprised 0.3% of circulating CD8⁺ T cells (range 0.02-1.4%), and 1.2% of CD4⁺ T cells (range 0.3-3%). Gut and skin ex-Trm were phenotypically similar; both expressed the residency associated markers CD9 and CD101 but lacked CD69 expression. Gut ex-Trm were phenotypically distinct from both the traditional gut-trophic population (α4β7+CD103-CD45RA) and from naïve T cells. The proportion of gut ex-Trm did not differ between health and IBD. However, gut-derived ex-Trm were significantly reduced, relative to skin-derived ex-Trm, in Crohn’s disease, but not ulcerative colitis, when compared with health.

A putative gut-derived ex-Trm population can be identified in both healthy and IBD peripheral blood, with IBD-associated changes identified in this population and intestinal Trm. Circulating ex-Trm could link discreet areas of intestinal inflammation in Crohn’s disease and there is a selective loss of the gut ex-Trm population from the blood of these patients. The role of ex-Trm in IBD merits further study.