The oral, selective Janus kinase inhibitor upadacitinib (UPA) has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Ulcerative Colitis (UC) in a Phase 3 clinical programme comprising two identical induction trials (U-ACHIEVE Induction [NCT02819635] and U-ACCOMPLISH [NCT03653026]) and a maintenance study (U-ACHIEVE Maintenance). This analysis assessed the impact of baseline corticosteroid (CS) use on the efficacy and safety of UPA in patients in these trials.

Patients were randomised 2:1 to UPA 45 mg once daily (QD) or placebo (PBO) for 8 weeks. Patients who achieved a clinical response at Week 8 were re-randomised 1:1:1 to UPA 15 mg QD, UPA 30 mg QD or PBO for 52 weeks. Here, we report induction and maintenance endpoints and safety data stratified by baseline CS use.

Baseline demographics and disease characteristics were generally well balanced across treatment groups, regardless of baseline CS use. Clinical remission rates among patients receiving UPA 45 mg induction therapy did not differ by baseline CS use (Figure 1A). In the induction period, rates of treatment-emergent adverse events of special interest (AESI), including serious and opportunistic infections, were increased in the UPA 45 mg plus baseline CS group compared with the PBO and UPA without baseline CS groups (Table 1). In the maintenance study, CS tapering was mandated. CS-free remission at Week 52 (defined as clinical remission, per Adapted Mayo Score, and CS free for ≥90 days immediately prior to Week 52) was significantly increased with UPA 30 and 15 mg compared with PBO (both p<0.001; Figure 1B). Among patients receiving UPA maintenance, rates of treatment-emergent AESIs in the baseline CS versus no baseline CS groups were 33% versus 39% and 27% versus 35% in the UPA 30 mg and UPA 15 mg groups, respectively. Malignancy, major adverse cardiovascular events, venous thromboembolic events, and serious and opportunistic infections were reported infrequently in patients receiving UPA (Table 1).

This post hoc analysis suggests that, in patients with moderately to severely active UC, UPA is superior to PBO in conferring CS-free remission. Baseline CS use was not associated with any apparent efficacy benefit and carried a potential increased safety risk. These results suggest that achieving early disease control with UPA and without CS use is an optimal treatment strategy for this population.

Educational objectives:
To discuss impact of COVID-19 pandemic on research activity for commercial and non-commercial studies in IBD
To consider lessons learned regarding efficient trial design
To propose future mitigation in event of further pandemic waves 

1.  to understand the prevalence and major types of EIMs in IBD
2. to understand the impact of EIMs on the disease course and relationship with disease activity in IBD
3. to review the management and therapeutic choices of EIMs in IBD
4. to summarize the evidence on specific drug classes in the treatment of IBD with EIMs (e.g. conventional therapies, steroids, anti-TNFs and new biological classes)
5. to review how the presence of EIMs may modify therapeutic decisions

Patients with IBD show distinct antibody responses, particularly against microbiota. However, a comprehensive overview of the antibody epitope repertoire in IBD is lacking. Here, we characterized serum antibody responses in patients with IBD and population controls using a high-throughput phage-displayed immunoprecipitation sequencing (PhIP-seq) workflow and associated these to disease phenotypes and the faecal microbiome.

PhIP-seq was leveraged to characterise antibody responses against 344,000 rationally selected peptide antigens in 497 patients with IBD which were compared with 1,326 individuals from a population-based cohort (Fig. 1A-B). Antibody profiles were linked to 23 IBD-specific clinical features such as disease location and surgical history and to faecal microbiota composition (Fig. 1C).

Patients with IBD demonstrated distinct antibody epitope repertoires compared with individuals from the general population, with 373 differentially abundant antibody-bound peptides (202 overrepresented, 171 underrepresented) belonging to bacterial flagellins (69), virulence factors (102), other antigens of both commensal and pathogenic bacteria (90) as well as viruses (67) and food proteins (24) (Figure 2). In particular, antibody responses against bacterial flagellins, many of which belong to Lachnospiraceae bacteria (e.g. Roseburia spp.), but also Eubacterium spp. and pathogens (e.g. Legionella, Clostridium, Burkholderia) dominated in patients with Crohn's disease (CD), and were associated with ileal disease involvement and more complicated disease behaviour (e.g. fibrostenotic disease, surgical history) as well as anti-Saccharomyces cerevisiae antibody positivity. Furthermore, many other antigens were newly identified, e.g. decreased responses to E. coli virulence factors and genome polyproteins of enteroviruses, and increased responses to food antigens (wheat, barley) and autoantigens (particularly collagen type I and VI). Antibody epitope repertoires were able to accurately discriminate CD from population controls (area under the curve [AUC]=0.88, test set evaluation), showing very high discriminative performance (positive and negative predictive value of 72% and 93%, respectively, representing predicted classes in test set) (Fig. 3A-C), which was less accurate for ulcerative colitis (UC) (Fig. 3D-F).

This study demonstrates the size, diversity and complexity of systemic antibody epitope repertoires in patients with IBD compared to controls, showing that distinct clinical phenotypes of IBD are characterized by unique antibody signatures. PhIP-seq is a powerful tool for identifying systemic immune-based biomarkers and exposing novel immunological targets in immune-mediated inflammatory diseases like IBD.

Patients with IBD show distinct antibody responses, particularly against microbiota. However, a comprehensive overview of the antibody epitope repertoire in IBD is lacking. Here, we characterized serum antibody responses in patients with IBD and population controls using a high-throughput phage-displayed immunoprecipitation sequencing (PhIP-seq) workflow and associated these to disease phenotypes and the faecal microbiome.

PhIP-seq was leveraged to characterise antibody responses against 344,000 rationally selected peptide antigens in 497 patients with IBD which were compared with 1,326 individuals from a population-based cohort (Fig. 1A-B). Antibody profiles were linked to 23 IBD-specific clinical features such as disease location and surgical history and to faecal microbiota composition (Fig. 1C).

Patients with IBD demonstrated distinct antibody epitope repertoires compared with individuals from the general population, with 373 differentially abundant antibody-bound peptides (202 overrepresented, 171 underrepresented) belonging to bacterial flagellins (69), virulence factors (102), other antigens of both commensal and pathogenic bacteria (90) as well as viruses (67) and food proteins (24) (Figure 2). In particular, antibody responses against bacterial flagellins, many of which belong to Lachnospiraceae bacteria (e.g. Roseburia spp.), but also Eubacterium spp. and pathogens (e.g. Legionella, Clostridium, Burkholderia) dominated in patients with Crohn's disease (CD), and were associated with ileal disease involvement and more complicated disease behaviour (e.g. fibrostenotic disease, surgical history) as well as anti-Saccharomyces cerevisiae antibody positivity. Furthermore, many other antigens were newly identified, e.g. decreased responses to E. coli virulence factors and genome polyproteins of enteroviruses, and increased responses to food antigens (wheat, barley) and autoantigens (particularly collagen type I and VI). Antibody epitope repertoires were able to accurately discriminate CD from population controls (area under the curve [AUC]=0.88, test set evaluation), showing very high discriminative performance (positive and negative predictive value of 72% and 93%, respectively, representing predicted classes in test set) (Fig. 3A-C), which was less accurate for ulcerative colitis (UC) (Fig. 3D-F).

This study demonstrates the size, diversity and complexity of systemic antibody epitope repertoires in patients with IBD compared to controls, showing that distinct clinical phenotypes of IBD are characterized by unique antibody signatures. PhIP-seq is a powerful tool for identifying systemic immune-based biomarkers and exposing novel immunological targets in immune-mediated inflammatory diseases like IBD.

The burden of inflammatory bowel disease (IBD) in health care is high and the incidence and prevalence rates of IBD in Finland are among the highest in the world.  Our aim was to assess the actual incidence and the trends of IBD in Finland during 2000-2020 using nationwide registry-based data. We also estimated the nationwide prevalence of IBD in 2000 and  2020.

This study included patients to whom IBD reimbursement was newly attributed between January 1, 2000 and December 31, 2021. Data were retrieved from the Social Insurance Institution of Finland.  Incidence and prevalence rates were calculated by dividing the number of annual new IBD cases by the size of the population at risk during each calendar year.

A total of 42,498 new IBD cases were identified during years 2000-2020; 31,372 with ulcerative colitis (UC) and 11,126 with Crohn’s disease (CD).The crude annual incidence per 100,000 increases in CD from 7.5 to 13.4 (IRR 1.02, CI 1.019 - 1.025) and in UC from 20.4 to 34.7 (IRR 1.03, CI 1.023 - 1.027) (Fig. 1). The crude prevalence of IBD increases from 376 to 972 per 100,000 (PRR 1.05, CI 1.046-1.047).Men have significantly higher incidence than women in UC (IRR 1.26, CI 1.228-1.284). In contrast, there is no difference between genders among CD patients (IRR 0.98, CI 0.95-1.02). In UC, the peak incidence occurs in the age group 25-29 (Fig. 2), whereas in CD, the incidence is
highest in slightly younger patients (Fig. 3). 

Figure 1. Incidence of ulcerative colitis and Crohn`s disease in Finland  during 2000-2020



Figure 2. Annual incidence of UC by age groups during 2000-2020





Figure 3. Annual incidence of CD by age groups during 2000-2020

During the first two decades of the 21st century, the incidence of UC and CD continues to increase in Finland, and almost one percent of the population has IBD.

Current knowledge regarding the epidemiology of pouchitis is based on highly selected, mostly single-center, patient cohorts. Our objective was to prospectively determine the population-based incidence of pouchitis in patients with ulcerative colitis (UC) in the first 2 years after ileal pouch-anal anastomosis (IPAA) and analyze time trends of the incidence of pouchitis.

We used national registries to establish a population-based cohort of all Danish patients undergoing proctocolectomy with IPAA UC between 1996 and 2018. The primary outcome was the development of pouchitis within the first 2 years after IPAA, evaluated by time period of IPAA. The period of IPAA was categorized as follows: 1996-2000 (pre-biologic-1), 2001-2005 (pre-biologic-2), 2006-2010 (early-anti-TNF), 2011-2014 (expanding anti-TNF), 2015-2018 (current biologic). Pouchitis was defined using a previously developed case-finding definition for use in administrative claims data. Kaplan Meier and Cox Proportional Hazard modeling were utilized in the evaluation of time to development of pouchitis.

We identified 1,664 patients that underwent an IPAA for UC. The cumulative incidence of pouchitis in the 2 years after IPAA increased throughout the study period, from 40% in 1996-2000, (95% CI:35%-46%) to 55% in 2015-2018, (95% CI:48%-63%, Table 1).  Patients undergoing surgery between 2015-2018 also demonstrated an increased risk of pouchitis compared to the earliest study period (1996-2000) after adjusting for sex, age, and socioeconomic status (Hazard Ratio [HR] 1.57, 95% CI:1.20-2.05, Table 2, Figure 1). In a separate model adjusting for the same clinical and demographic factors, there was no significant relationship between the preoperative use of anti-tumor necrosis factor alpha therapy use and the risk of pouchitis when evaluated in the entire population (HR 1.14, 95% CI:0.93-1.40) and when evaluated by time period of surgery. 

This first population-based study demonstrated a 15% absolute and 38% relative increase in the incidence of pouchitis among patients undergoing surgery between 1996 and 2018, with the greatest cumulative incidence of pouchitis demonstrated in the most recent era (2015-2018). The striking increase in the incidence of pouchitis highlights the need for further research into causes and prevention of pouchitis.

1. Define the various risk factors for serious infection and opportunistic infections
2. To go over the various immunosuppressive medications that are routinely used and review the evidence with regards to risk for infection.
3. To assess the various single medications and risk of infection
4. To assess the risk of infection with dual and triple immunosuppressive therapy
5. Prevention of infection through screening and vaccination

Limited data is available of the outcome of inflammatory bowel disease (IBD) in patients with solid organ transplantation (SOT). The aim of our study was to describe the natural history of pre-existing IBD and de novo IBD after SOT.

A retrospective, observational, multi-centre, nationwide study was designed. IBD patients with SOT were included. We identified two separate cohorts: (1) patients with pre-existing IBD at the time of SOT and (2) patients without IBD at the time of SOT (de novo IBD). The primary outcome was IBD progression, defined by the escalation of medical treatment, surgical therapy for medically refractory IBD or IBD-related hospitalization during follow-up. Risk factors were identified using multivariate Cox proportional hazard analysis.

A total of 177 patients (106 pre-existing IBD and 71 de novo IBD) from 31 centres were included. Baseline characteristics are shown in Table 1. Eighty-six patients with IBD and SOT underwent liver transplantation, while 82 required renal, 4 lung, 3 heart, 1 liver/kidney and 1 pancreas/kidney transplantation.

Pre-existing IBD patients were followed-up over a median of 4.8 years (range 2.6-9.4). At the time of SOT, 61 patients (59.8%) were not under maintenance treatment or were treated with 5-aminosalicylates, 10 (9.8%) were on immunosuppressive therapy and 31 (30.4%) were receiving biological agents, of which 8 were on combo therapy. At the moment of SOT, only 8 patients (7.5%) had moderate IBD activity whereas the remaining patients were in remission. During follow-up 33.7% of patients with pre-existing IBD had disease progression, with a median time between SOT and IBD progression of 2.2 years (range 1.3-4.6). No differences between Crohn´s disease and ulcerative colitis were found (Figure 1).

The median time of follow-up in de novo IBD group was 5.1 years (range 2.1-8.2). In this cohort, 55.9% of patients had disease progression during follow-up (Figure 2), with a median time to flare of 1.9 years (range 0.8-3.9) from diagnosis.

In pre-existing IBD cohort, multivariate Cox-regression analysis identified active IBD at the time of SOT (HR=1.80; 95%CI: 1.14-2.84; p=0.012) and the presence of extraintestinal manifestations (HR=3.10; 95%CI: 1.47-6.54; p=0.003) as predictive factors of IBD progression after SOT.

One third of patients with pre-existing IBD have disease progression, needing medical therapy escalation, surgery or hospitalization after SOT. Active IBD at the time of SOT and the presence of extraintestinal manifestations were identified as risk factors for disease progression. In de novo IBD cohort, about half of patients showed disease progression during follow-up.

Monitoring of monoclonal antibody clearance has been hypothesised to be an appealing approach for predicting treatment outcomes in patients with inflammatory bowel diseases. We aimed to investigate the benefits of monitoring infliximab and ustekinumab clearance in patients with Crohn’s disease (CD) based on data from clinical trials.

Data were obtained from patients with moderate-to-severe CD starting infliximab (n=108)¹ or ustekinumab (n=80)² therapy. Endoscopic remission (CD Endoscopic Index of Severity <3) and endoscopic response (≥50% decrease from baseline in simple endoscopic score for CD) were assessed at week (w)12 and w24 of infliximab and ustekinumab therapy, respectively. A priori prediction (based on covariate data only; at w0) and a posteriori prediction (Bayesian forecasting using measured drug concentrations; during treatment) were performed using previously built population pharmacokinetic models (NONMEM 7.5).^3,4 Covariates of fecal calprotectin, albumin, CD activity index, and antibodies towards infliximab (ATIs) were used to estimate infliximab clearance. Albumin and body weight were used to estimate ustekinumab clearance.

Patients achieving endoscopic remission at w12 had significantly lower infliximab clearance and higher infliximab serum concentration at w2 and w6 of treatment (P <0.05, Table 1). Patients achieving endoscopic response at w24 had significantly lower ustekinumab clearance at w4 and w8, as well as a significantly larger reduction in clearance relative to w0 (P <0.05, Table 1). However, ustekinumab serum concentrations at w4 and w8 were similar between patients with and without endoscopic response (P >0.2, Table 1).
Most patients with an early increase in infliximab clearance (16/22; 73%) and ustekinumab clearance (27/29; 93%) did not reach the endoscopic endpoint (P <0.05; Table 2). However, a decrease in clearance was no guarantee for endoscopic remission during infliximab therapy (false predictive rate 46%) and response during ustekinumab therapy (false predictive rate 69%).
The infliximab clearance after start of induction therapy (at w2 and w6) was significantly higher in patients who developed ATIs during induction therapy (Figure 1).

Lower infliximab and ustekinumab clearance (absolute as well as relative to w0) early during induction predict more favourable endoscopic outcomes. In patients treated with ustekinumab, clearance monitoring may better predict endoscopic response at w24 as compared to standard therapeutic drug monitoring.

References
1. D'Haens et al.Gastroenterology 2018
2. Verstockt et al. J Crohns Colitis 2019.
3. Dreesen et al. Br J Clin Pharmacol 2021.
4. Wang et al. Br J Clin Pharmacol 2021.

1. To understand the key tests and investigations that complete the work up of the presenting symptoms 
2. To understand the scope of factors that affect IBD patients and which patients need to be educated about 
3. To learn the principles of a collaborative approach when initiating a treat-to-target treatment strategy 
4. To recognise the different factors that affect quality of life for an IBD patient and to develop a patient-centred approach to improvement in quality of life. 

Ritlecitinib (PF-06651600) is an oral Janus kinase 3/TEC inhibitor, demonstrated to be safe, well-tolerated and efficacious in moderate to severe active ulcerative colitis. The aim of this pre-specified biomarker study was to develop serum signatures that could serve as non-invasive indicators of endoscopic improvement and histologic remission after ritlecitinib therapy.

Colon biopsies and peripheral blood were obtained from participants for biomarker profiling before and after receiving 8-week induction therapy with oral ritlecitinib (20mg,70mg, 200mg, or placebo N=39, 39, 33, 18 respectively) once daily. Responders were defined by endoscopic improvement (Mayo endoscopic sub-score <=1) or histologic remission (Geboes Score ≤ 3.0). RNA from colon biopsy samples were processed using RNA sequencing (Fulgent Therapeutics, CA). Serum proteins were measured using the Olink Explore Inflammation panel (Olink, Proteomics, Sweden). Linear mixed models were used to estimate the change from baseline (CFB) of each protein/gene at Week 8 by treatment and clinical response. Differences between response groups and treatment arms were also analyzed.

Analysis of serum revealed 37 proteins significantly changed at week 8 compared to baseline in responders (FDR < 0.05). Changes in four of these proteins (IL4R, TNFRSF4, SPINK4 and LAIR-1) correlate with both endoscopic improvement and histological remission and were able to separate responders from non-responders AUC (area under the ROC curve) = 0.71 [0.61-0.81] based on endoscopic improvement and AUC = 0.60 [0.48-0.71] based on histological remission). To determine if these 37 proteins reflect tissue inflammation, we evaluated the differential expression of genes encoding these proteins with RNA-seq of inflamed biopsies. Ten genes (CXCL1, FCAR, CKAP4, SPINK4, CXCL17, OSM, CD4, CXCL9, IL17A, GZMB) had significant changes from baseline between responders and non-responders at Week 8 (FDR < 0.1) in either endoscopic improvement or histological remission. Furthermore, these ten genes were significantly increased at baseline between inflamed and non-inflamed colon biopsies.   

Finally, colon biopsy transcription levels of TNFRSF4, SPINK4 and LAIR1 were modulated with marginal significance (P-value < 0.1) in either endoscopic improvement or histological remission at Week 8.  

Serum proteomics revealed a promising signature of endoscopic improvement and histologic remission in UC participants treated with ritlecitinib. Changes in a subset of these serum proteins parallel tissue gene expression and offer insight into a potential non-invasive companion monitoring test to guide clinical management of patients treated with ritlecitinib.

Video case demonstration with the application of intestinal ultrasound disease activity scoring.

Learning objectives

At the end of this workshop participants should be able to know:

• ·        Key quality indicators for a good report for intestinal ultrasound (IUS)
• ·        How to assess and how to report intestinal inflammation in IUS
• ·        Relevant findings for inflammation/complications in IUS that should be described in a report
• ·        Cine loops with UC and CD IUS-pathologies will be demonstrated together with the corresponding reports

Interactive cases will be presented to illustrate IUS diagnosis of UC complications, such as acute severe colitis, including monitoring of response to treatment, perforation, chronic structural damage in UC, infectious colitis, pseudopolips and lymphoma. 

Crohn’s disease (CD) is predominantly allocated within the small bowel and characterized by persistent chronic inflammation that may cause an extramural complications. Intestinal Ultrasound (IUS) has shown to be highly effective in detecting and determining CD related complications such as Strictures, fistulas, and inflammatory masses. The aim of this interactive presentation is to show the use of IUS in some real clinical cases.

Inflammatory bowel disease (IBD) is a complex disease characterised by chronic inflammation of the digestive tract. Genome-wide association studies (GWAS) have identified 241 risk loci significantly associated with the two common forms of IBD, Crohn’s disease and ulcerative colitis. The vast majority of these risk loci reside in non-coding regions of the genome, and we only know which gene is dysregulated to increase risk of disease for a minority. This knowledge gap makes it difficult to draw insights into disease pathology and identify new candidate drug targets.

To improve biological insights from IBD GWAS, we generated single cell RNA-sequencing data from ileal biopsies ascertained from 25 CD patients with active ileal inflammation and 26 non-IBD controls. We identified 49 different cell types among the ~140K sequenced cells (Fig.1), including all major immune, enterocyte, secretory and mesenchymal populations. Our optimized single-cell dissociation protocol preserves the top of villus epithelial cells, which are inherently prone to anoikis, enabling generation of high-quality transcriptomes for the first time. 

Fig. 1
Single-cell atlas of terminal ileum biopsies from Crohn’s disease and non-IBD individuals.

We identified 797 unique genes differentially expressed between CD patients and controls, with notable expression differences in stem cell, secretory, and enterocyte populations. Genes involved in antigen presentation and interferon-gamma signaling were enriched among those most frequently dysregulated cell types. In an attempt to identify which of these expression differences are likely causal of disease, rather than simply a consequence of it, we integrated results from the latest IBD GWAS to assess the extent to which genes captured disease heritability, and in which cell-types. Genes specifically expressed in Tregs, monocytes and IL10RA-negative monocyte-derived macrophages captured a significant fraction of disease heritability, strongly implicating these cell types in disease pathogenesis. We investigated which genes were driving these enrichment signals and identified candidate effector genes at many IBD risk loci. Reassuringly, many confirmed IBD effector genes known to have a role in the normal functioning of these cell types were found, including NOD2, IL18RAP, IL23R, NCF4, and IL2RA.

Single-cell analysis combined with IBD genetics has generated strong evidence for a causal role of novel disease mechanisms that have therapeutic potential. Further experiments are underway to validate this finding. At ECCO we will present an updated version of this analysis, including genetic mapping of gene-regulation across cell types to identify IBD effector genes and causal variants.

Environmental factors play an important role in the pathogenesis of IBD. Thereby the question: can we modulate these factors and impact the disease course?
A lifestyle change including physical activity and diet can be beneficial for patients with IBD. 

The main objective of this presentation is to review recent data from intervention trials supporting this lifestyle change in patients with IBD.

T resident memory (Trm) cells in the intestinal mucosa and in particular subpopulations expressing phenotypic markers such as alphaE-beta7 or NKG2D have been associated with chronic inflammatory bowel disease (IBD) activity. We hypothesize that these populations may have a direct deleterious impact on the intestinal epithelium in IBD.

The phenotypic study of mucosal lymphocytes was performed in two prospective cohorts: ELYP including patients with active IBD before initiation of biotherapy and REMIND including patients with ileal Crohn's disease (CD) requiring ileocaecal resection. These analyses were performed before initiation of treatment and one year after continuous therapy in the ELYP cohort and on the resection specimen in the REMIND cohort. An innovative ex vivo autologous organoid-mucosal T cell coculture model was developed using the REMIND cohort specimens for patients and healthy ileum from individuals without IBD for controls (Figure 1). T cell infiltration within the organoid and epithelial cell death were assessed by confocal microscopy. A panel of 30 cytokines was quantified in the supernatants of cocultures.


Figure 1

In the ELYP cohort, before the start of treatment, IBD patients had lower expression of alphaE-beta7 and NKG2D on mucosal CD8 T cells. While alphaE-beta7 and NKG2D expression on mucosal CD8 T cells had returned to normal in endoscopic responders, it remained decreased in non-responders. Similarly, the inflammatory mucosa of the REMIND surgical specimens had lower levels of CD4 and CD8 T cells expressing alphaE-beta7 and NKG2D compared with controls and non-inflamed regions. We developed a coculture model between mucosal lymphocytes and organoids generated under autologous conditions. We showed an increase in apoptotic cell death in epithelial cells from CD patients which was not found in control cocultures. There was a significant correlation between the degree of epithelial cell death and T cell infiltration (Figure 2). Various proinflammatory cytokines such as IFNgamma, TNFalpha, IL-6 and IL- 17a were also increased in the supernatants. The use of antibodies blocking the alphaE-beta7 and NKG2D pathways of interest inhibited this effect by different mechanisms (Figure 3) While anti-beta7 and anti-NKG2D had comparable effects in terms of cell death inhibition, only anti-beta7 reduced T cell infiltration. Anti-NKG2D had no effect on cell infiltration but a reduction of perforin was observed in the supernatants.

Figure 2

Figure 3
CC= Coculture

These data demonstrate for the first time the direct cytotoxic deleterious effect of mucosal T cells on the epithelium of CD patients using a novel coculture model. AlphaE-beta7 and NKG2D pathways appear to be relevant in this process.