bluuebunny/crossref_metadata_2025 huggingface dataset:
P085 Deep profiling of the circulating immune cell landscape in inflammatory bowel disease by mass cytometry
Authors: Horn V , Borek Z , Mantzivi E , Urbicht M , Boesel D , Baumgart S , Sonnenberg E , Lissner D , Siegmund B , Mei H , Hegazy A N
Published: January 2020

Background

A complex interplay of innate and adaptive immune cells maintains intestinal homeostasis. In inflammatory bowel disease (IBD), the fragile balance between regulatory and inflammatory cell subsets breaks down. The latter are recruited to the gut where they sustain intestinal inflammation and lead to tissue destruction. Due to re-circulation and gut-homing processes, the circulating immune cell compartment experiences profound changes that reflect disease activity. Meanwhile, single-cell techniques like mass cytometry have become a powerful technology to shed a light on the heterogeneity and dynamics of immune cells. As obtaining intestinal biopsies from inflamed gut is invasive and poses patients at risk, diagnostics and therapy monitoring from ‘liquid biopsies’ would be a great advance. A deeper understanding of the circulating immune cell landscape in IBD pre- and post-treatment could significantly contribute to IBD patient management by early prediction of therapy response.

Methods

Whole blood from 24 IBD patients—including 16 ulcerative colitis (UC) and 6 Crohn’s disease (CD) patients before treatment—and 18 age- and sex-matched healthy donors (HDs) was incubated with proteomic stabiliser and frozen. Upon thawing, cell suspensions were Palladium barcoded, stained with a 37-marker panel and acquired on a Helios mass cytometer. The generated dataset was normalised, de-barcoded and subsequently analysed.

Results

Using dimensionality reduction and neural-network-based algorithms, we faithfully identified different circulating immune subsets in healthy donors and IBD patients. Our preliminary analysis revealed altered myeloid cell populations, like neutrophils and macrophages, in IBD patients. In line with an activation of the innate immune system, we observed a considerable increase in the neutrophil compartment compared with healthy donors. Moreover, patterns of marker expression within different subsets showed substantial differences between healthy donors, CD and UC patients.

Conclusion

Here, we show a mass cytometry panel that identifies the circulating immune cell landscape and shows major differences between healthy donors, CD and UC patients.
P086 Identification of constitutive modifications in plasma cells and B lymphocytes in patients with inflammatory bowel disease
Authors: Marin A C , Fernández-Tomé S , Ortega Moreno L , Martin Dominguez V , Casabona S , Becerro I , Mora-Gutiérrez I , Villacañas-Gil I , Baldan-Martin M , Moreno-Monteagudo J A , Santander C , Chaparro M , Bernardo D , Gisbert J P
Published: January 2020

Background

Plasma cells (PCs) and B lymphocytes (BLs) are a source of immunoglobulins (Ig), being IgA essential for intestinal homeostasis. An unbalanced intestinal Ig production has been described in inflammatory bowel disease (IBD). Nevertheless little is known about the role of mucosal Ig-producing BL and PC in IBD, reason why we decided to study them.

Methods

We included 12 healthy controls -HC-, 10 patients with ulcerative colitis (three active -aUC- and seven quiescent -qUC) and 10 patients with Crohn’s disease (three active -aCD- and seven quiescent -qCD). Disease was located in the distal colon in all patients, although the quiescent ones had no inflammation (endoscopic Mayo = 0; SES-CD = 0–1). Distal colon biopsies were collected together with peripheral blood. Mucus layer and epithelial barrier was removed from the biopsies and lamina propria mononuclear cells were harvested using the ‘walk-out’ protocol. Peripheral blood mononuclear cells were obtained after ficoll centrifugation. In both cases, cells were stained with specific antibodies, acquired in a FACSCanto II cytometer, and analysed with FlowJo. Median percentage of PC and BL (and their subsets) relative to each tissue was calculated and compared using non-parametric statistics, considering statistically significant p < 0.05.

Results

The proportion of plasmablasts, blood-precursors of PC, was higher in the blood of active IBD patients (HC: 0.8%; aUC: 5.3%; aCD: 3.4%). Even though there were no differences in the colonic proportion of PC between the study groups, there was a constitutive lower proportion of IgA-producing PC in IBD, irrespective of its type (UC or CD) or presence of inflammation (HC: 88%; qUC: 55%; aUC: 38%; qCD: 70%; aCD: 44%). Moreover, aCD patients also showed a significantly higher proportion of IgM-producing PC (HC: 6% vs. aCD: 10%), and a higher proportion PC expressing CD19 compared both with HC and qCD (HC: 43%; qCD: 52%; aCD: 74%). The proportion of BL and their subsets did not show differences between the study groups, neither in blood nor in colon. However, in UC patients, some circulating subsets displayed a lower proportion of cells expressing the gut-homing integrin β7: naive BL (HC: 11.5%; qUC: 2.9%; aUC: 0.6%) and IgM memory BL type CD27+ (HC: 43%; qUC: 30%; aUC: 23%) and also CD27- (HC: 32% vs. aUC: 5%).

Conclusion

IBD patients have a diminished percentage of colonic IgA-producing PC, which is irrespective of the type of IBD or the inflammatory status; this reduction could compromise the correct microbiota regulation in IBD. The reduction of the percentage of β7-expressing BL in the blood of UC patients could potentially point to a specific pathogenic mechanism of UC.
P089 Immune system cell differences between Crohn’s disease and ulcerative colitis patients in remission under anti TNF treatment
Authors: Notararigo S , Viñuela Roldán J E , Quiroga A , Dominguez-Munoz J E , Barreiro-de Acosta M
Published: January 2020

Background

Inflammatory bowel disease (Crohn’s disease (CD) and ulcerative colitis (UC)) are chronic gastrointestinal disorders of unknown aetiology where the immune system dysregulation is the responsible for immunological imbalance characterised by a relevant production of pro-inflammatory cytokines. The tumour necrosis factor-α (TNF-α) plays a central role in the mucosal inflammation, recruiting and over stimulating other immune system cells like Th1. The aim of this study is to describe CD4+T cells sampled in fresh peripheral blood in IBD patients and in healthy controls (HCs) to estimate the effect of IFX on peripheral immune system cell subtypes.

Methods

A pilot case–control study was performed. Inclusion criteria were IBD patients in clinical remission under maintenance IFX treatment. Remission was defined as a Partial Mayo <2 in UC and a Harvey–Bradshaw <4 in CD. The inflammation patient’s condition was measured by C-reactive protein (CRP) and Calprotectin. After informed consent, blood samples were obtained in IBD patients just before IFX infusions and in HC. Participants were classified in different groups (1) HC, (2) CD and (3) UC. To investigate the immune system cell subtype, PBMCs were isolated from fresh blood in order to characterise: monocyte, dendritic cells (DC), Th1, Th17, Thf and Th1/Th17. Cells were then incubated with specific fluorescent antibodies’ cocktails, then identified with flow cytometry. We spotlight on DC and monocyte, in order to characterise the plasticity of both.

Results

Thirty-two participants were consecutively included 13CD, 9UC, mean age 43, all in remission under IFX maintenance therapy and 10 HC. Mean CRP was 0.08 mg/dl and 99.5 µg/g. Th1 CD4+CXCR3+increased in UC than CD patients, showing a tendency reaching a relative value of 45% vs. 34% of HC, nevertheless the expression of CCR5 maintained normal value in both groups. Th17 CD4+CCR6+CD161+significantly increase in CD and UC groups vs. control, indeed the Th17/Thf CD4+CCR6+CXCR5+showed higher expression in UC patients, as well as the Thf subtype CD4+CXCR5+conduct. Th1/Th17 CD4+CXCR3+CCR6+belonging to Th17 subtype showed a tendency to rise in UC with a relative value of 23% vs. 19% HC. DC did not show difference in Myeloid subtype CD11C+and Precursor CD11C+CD123low. Plasmacytoid CD11C+CD123+increased significantly in UC with a relative value of 6.5%. Monocyte M3 CD14−CD16+ revealed itself to be higher in UC than in CD.

Conclusion

The immune system cell subset is highly modified by the IBD disease type (CD,UC) despite being in remission under IFX therapy. Th1 levels are significantly augmented although their reactivity is not altered by CCR5 detection. Plamacytoid DC cell increases in UC patients if total amount of CD11C+ CD diminishes.
P100 CD161 levels are reduced in all subpopulations of T-cell colonic mucosal lymphocytes in inflammatory bowel disease
Authors: Tristan E , Carrasco A , Martín-Cardona A , Zabana Y , Aceituno M , Raga A , Andújar X , Arau B , Ruiz-Ramírez P , Ruiz-Campos L , Fernández-Bañares F , Esteve M
Published: January 2020

Background

CD161 is a type C lectin expressed in NKs cells and peripheral T cells (TCRγδ and αβ, NKTs), enriched in intestinal populations. Its expression can be modulated by infections and inflammation. MAIT cells are a subset of innate antimicrobial T-cells abundant in the mucosa but their role in immunological regulation is still unknown.

Aim

To measure CD161 levels in subtypes of T-lymphocytes of intestinal mucosa: CD4+, CD8+, double positive (DP,CD4+CD8+), double negative (DN,CD4−CD8−), MAIT cells (CD161+TCRVα7.2+) and intraepithelial cells (CD103+)

Methods

Twenty-six patients with active inflammatory bowel disease (IBD) without immunosuppressive treatment (n = 9 Crohn’s disease -CD- colon, 9 CD ileum, n = 8 ulcerative colitis -UC- and 10 healthy controls (paired biopsies of ileum, right and left colon) were included. Lymphocyte subpopulations were analysed with LSRFortessa cytometer. Non-parametric Kruskal–Wallis test was applied. Results are expressed as % of median (25–75%IQI).

Results

In healthy mucosa, we did not find differences related to location in any of CD161 subpopulations except for increase of CD3+CD161+CD103+ and decrease of CD3+CD161+CD103− in left colon compared with right colon and ileum. Regarding MAIT cells, a progressive decrease was observed in distal parts of intestine for CD3+MAIT+CD103+ while CD3+MAIT+CD103− subpopulation has a specular behaviour; CD3+CD8+MAIT+ was increased in ileum compared with colon (Table 1).

Conclusion

There is a regional specialisation for the subset CD103+ of both CD161+CD103+ and MAIT_CD103+ cells in healthy intestine. CD3+CD161+ T cells are reduced in IBD colonic inflammation and could serve as a marker of active IBD but not to sort between CD and UC.
P102 Host gene background and concentration influence the butyrate effect on modulating IECs proliferation
Authors: He H , Hu J , Wang W , Zhang M , Zheng M , Peng X , Zhang Y , Zhou M , Liu T , Zhao J , Zhang Q , Zhi M
Published: January 2020

Background

Intestinal epithelial barrier dysfunction is a major pathological feature of inflammatory bowel disease (IBD). Stability and accuracy of intestinal epithelial cells (IECs) self-renew are the fundament of intestinal mucosal regeneration and repair. Fermentable dietary fibre and short-chain fatty acid (SCFA) play a role in cell proliferation, histone acetylation and immune responses. However, the results about SCFA modulating IECs proliferation are not coincided. There are several reason that SCFA can have an impact on IECs through immune cell in animal experiment and that also include animal gene background, SCFA concentration, cell types used in cell experiment l. So we adopted intestinal organoids to investigate the effect of butyrate on IECs self-renew to avoid the immune cell influence and signal type cell experiments limitation.

Methods

Six to 8 weeks wide-type mice and IL10−/− mice were used. Mouse intestinal crypt isolation and organoid culture were according to previously published methods (H. Clevers et al., Gastroenterology 2011). Re-suspended isolated ISCs were seeded onto 10 ml MatrigelTM (Corning 356237) in CellCarrier-96 Ultra Microplates per well (Perkinelmer 6055302). Sodium butyrate (SB) was administered at a final concentration (from 0 to 0.2mM) at Day1. Organoids’ cross-sectional area was measured and calculated, as well as all images were captured using an Operetta High-Content Imaging System and Harmony software 4.8.

Results

SB promoted intestinal organoids proliferation in a narrow effective concentration from 0.02 to 0.09 mM (Figure 1). The effective SB concentration applied to WT mice-derived organoids other than IL10−/− mice-derived organoids. SB can effectively and rapidly promote organoid proliferation (Figures 2 and 4). SB can continuously promote the proliferation of organoids-derived organoids (Figures 3 and 4).

Conclusion

There is a narrow effective SB concentrationpromotes WT mice-derived organoids other than IL10−/− mice-derived organoids. This result may be used to illustrate the phenomenon that IBD-associated microbiota and metabolites, butyrate, has different effects on IBD patient and IBD model mice.
P111 Elucidation of inflammatory infiltration of myenteric plexus in IBD
Authors: Wiese J J , Fascì A , Kühl A A , Siegmund B , Prüß M S , Schumann M
Published: January 2020

Background

Since IBD is frequently associated with chronic abdominal pain and visceral hypersensitivity, affections to the sensory nerves within the ENS appear to be pivotal. In both inflammatory bowel diseases, i.e. the transmural inflammation of Crohn’s disease (CD) and the inflammation restricted to the colonic mucosa in ulcerative colitis (UC) infiltrations of the plexus by immune cells occur. However, the type of immune cells involved is so far unknown. Therefore, we characterised the immune cell infiltrations of myenteric plexus (MP) in CD and UC compared with controls.

Methods

We identified 12 IBD patients (four CD and eight UC) and four controls that had received surgery (ileocecal resections or colectomy). The severity of the disease was assessed by Mayo score, HBI score and questionnaires (Visual Analogue Scale, Pain Catastrophizing Scale, Inflammatory bowel disease quality of life and Irritable Bowel Symptom Severity Scale). Formalin-fixed, paraffin-embedded tissue was stained by classical immunohistochemistry. To identify myenteric plexus tissue was stained for CGRP and PGP9.5. Immunostainings for immune cells (T cells: CD3, CD4, CD8, Foxp3; B cells: CD20; monocytes/macrophages: CD68 and CD163) were analysed by quantifying within the plexus and within a defined area of 100 µm around the plexus.

Results

The mean size of myenteric ganglia in controls was found to be 0.100 ± 0.004 mm² and was significantly decreased in CD (0.055 ± 0.002 mm²) and UC (0.079 ± 0.004 mm²). The population of CD4+ T-cells, macrophages and monocytes within ganglia of the MP were unchanged in CD, UC. However, infiltrates within and around MP contained significantly more CD3+ T cells in CD (121 ± 63 intraganglionic cells/mm² and 1858 ± 1133 periganglionic cells/mm²) and UC (133 ± 80 intraganglionic cells/mm² and 1198 ± 693 periganglionic cells/mm²) compared with controls (28 ± 38 intraganglionic cells/mm² and 342 ± 93 periganglionic cells/mm²). This appeared to be secondary to a significant increase of periganglionic CD8+ T cells in UC (342 ± 293 cells/mm² compared with 164 ± 140 cells/mm² in controls) (see Figure 1) and secondary to a significant increase of periganglionic Foxp3+ T cells in CD (528 ± 193 cells/mm² compared with 0 ± 0 cells/mm² in controls). Moreover, CD20+ B cells were significantly increased in CD (528 ± 193 periganglionic cells/mm² compared with 0 ± 0 periganglionic cells/mm² in controls).

Conclusion

The intra- and periganglionic infiltrate of MP in inflammatory bowel disease contains CD3+CD8+ T cells in UC and CD3+Foxp3+ regulatory T cells as well as B cells in CD.
P113 Serum adipokines as non-invasive biomarker in Crohn’s disease
Authors: Ortega Moreno L , Sanz-Garcia A , Fernández de la Fuente M J , Arroyo Solera R , Chaparro M , Fernandez-Tome S , Marin A C , Mora-Fernandez I , Fernandez P , Baldan-Martin M , Bernardo D , Gisbert J P
Published: January 2020

Background

Adipose tissue wrapping the gastrointestinal tract is a risk factor for disease activity in Crohn’s disease (CD). Indeed, adipokines associated to lipid metabolism can modulate local immune responses. However, few studies have investigated the possible association between adipokines and CD. Here, we aimed to evaluate the role of serum adipokines as possible biomarkers in CD.

Methods

Serum samples were obtained from 18 patients with endoscopically active CD (aCD), 22 patients with endoscopically quiescent CD (qCD) and 36 non-inflamed healthy controls (HC). Serum leptin, ghrelin, resistin and adiponectin were analysed by Multiplex (Bio-Rad, Hercules, CA) in a Luminex 200 system technology. Adipokines means for each group of patients were compared and adjusted by Bonferroni or Wilcoxon tests. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were carried on to evaluate the discriminatory capacity of the adipokines levels between patients groups. Furthermore, for those adipokines that showed an AUC > 0.7, a binary logistic regression adjusted by possible confounders (i.e. sex, age and BMI) was performed in order to test their possible association with CD.

Results

No differences were found in age, sex or BMI among aCD, qCD and HC; there was no correlation either among the adipokines analysed. Means distribution for serum resistin was different among aCD, qCD and HC (p = 0.006). However, only comparisons between HC and aCD groups showed significant differences (p = 0.02) in the post hoc test. Serum leptin, ghrelin and adiponectin did not show differences between means. ROC curve for resistin showed an AUC of 0.78, with a standard error (SE) of 0.067 when HC and aCD groups were analysed (Figure 1). Furthermore, in this case, as sensitivity and specificity for Youden index correspond to the resistin median concentration, this value was selected as a cut-off for the binary logistic regression analysis; thus, odds ratio (OR) along with their 95% confidence interval (CI) analysis of high relative resistin levels (values higher than their median) adjusted by age, sex and BMI yielded a value of 5.46 (1.34–22.14) when aCD group was compared with HC group. Comparison between qCD and aCD showed an AUC of 0.70 with an SE of 0.089. However, ROC curve did not show a good accuracy when HC and qCD groups were analysed (AUC = 0.58; SE = 0.08). ROC curves analysis for leptin, ghrelin and adiponectin did not show enough accuracy to discriminate between groups.

Conclusion

Resistin may modulate the inflammation state in CD and it is probably associated to activity, being this association independent of sex, age or BMI.
P114 A screening tool for the early diagnosis of extraintestinal manifestations in inflammatory bowel disease: the EMAIL questionnaire
Authors: Busacca A , Ingrassia Strano G , Giuffrida E , Guida L , Scrivo B , Carrozza L , Calvaruso V , Cappello M
Published: January 2020

Background

Data on prevalence of extraintestinal manifestations (EIMs) in inflammatory bowel disease (IBD) range from 6% up to 47%. Recently, several red flags and questionnaires have been proposed for early diagnosis of articular manifestations. Our aim was to analyse the prevalence of EIMs in a single-centre prospective cohort, using a comprehensive questionnaire developed by our group to detect all EIMs (EMAIL questionnaire).

Methods

Patients with IBD attending our Clinic from November 2017 to January 2019 were interviewed using a two-part questionnaire, the first part for clinical-demographic data and the second part for EIMs. Patients positive to screening were referred for multidisciplinary approach.

Results

Two hundred and six IBD patients were interviewed, 114 (55.3%) Crohn’s disease (CD) and 92 (44.7%) ulcerative colitis (UC), 52.4% male, mean age 46.7 years (SD ± 15,2). Sixty (53%) CD patients and 48 (52%) UC patients, in total 108, had history of at least one EIM. Articular EIMs were found in 49 patients (24%); peripheral arthritis was found in 14% (29/206), axial arthritis in 9.7% (20 patients): seven patients (3.4%) had ankylosing spondylitis, 13 (6.3%) sacroiliitis. Cutaneous EIMs were detected in 39 patients (19%), erythema nodosum in 15 patients (7.3%), pyoderma gangrenosum in 9 (4.4%), psoriasis in 15 (7.3%) and folliculitis in 7 (3.4%). Ocular EIMs were observed in 35 patients (17%): uveitis in 7 patients (3.4%), conjunctivitis in 8 (3.9%), optic neuritis in 2, glaucoma in 2 patients, cataract in 13 (6,3%), dry eye in 4 (1.9%), central serous chorioretinopathy in 1. Hepatobiliary EIMs were observed in 31 patients (15%): 26 steatosis (12.6%), 5 (2.4%) primary sclerosing cholangitis. Four (2%) patients had DVT. Articular EIMs were more frequent in CD patients (p = 0.001). Skin manifestations were more frequent in female (p = 0.002) in CD (p = 0,032) and related with IBD activity (<0.001). Hepatobiliary manifestations were more frequent in male (p = 0,017) and in UC (p = 0,044). There was a significant correlation between DVT and IBD activity (p = 0,016).

Conclusion

The questionnaire developed by our group proved to be a sensitive screening tool. Articular and cutaneous EIMs are more frequent in CD, hepatobiliary EIMs are more frequent in UC. A gender difference has been found since cutaneous EIMs are more frequent in females, hepatobiliary more in males. Cutaneous EIMs and DVT are related with IBD activity.
P117 Biomarkers of extracellular matrix remodelling are associated with intestinal fibrosis assessed by magnetic resonance enterography and accumulated intestinal damage (Lémann index): the IBSEN study
Authors: Mortensen J , Lunder A K , Manon-Jensen T , Karsdal M A , Nielsen M J , Leeming D J , Hov J R , Negård A , Jahnsen J , Moum B , Vesterhus M , Høivik M L , Kristensen V A
Published: January 2020

Background

Magnetic resonance enterography (MRE) has become an important tool in the diagnosis and follow-up of Crohn’s disease (CD). MRE findings are used in the calculation of the Lémann index (LI), a score that quantifies accumulated bowel damage. However, calculating the score is demanding; thus, serum biomarkers reflecting tissue damage and fibrosis are warranted for monitoring purposes. Increased extracellular matrix (ECM) remodelling and collagen tissue deposition is the result of accumulated bowel damage, eventually leading to intestinal fibrosis; particularly, the basement membrane and interstitial matrix are affected. We aimed to investigate ECM serum biomarkers of type III collagen formation (PRO-C3), type IV collagen degradation (C4M), degradation of citrullinated vimentin (VICM) and their association with LI and the degree of bowel wall fibrosis assessed by contrast-enhanced MRE in CD patients.

Methods

Serum from CD patients was analysed (n = 85, part of IBSEN population). Competitive ELISA was applied for the quantification of PRO-C3, C4M and VICM in the serum samples. The LI score was calculated based on the surgical history, MRE findings and the endoscopy findings. The suggested cut-off for substantial bowel damage is LI >/= 2. Increased contrast enhancement of the bowel wall at 5 min and the presence of stenosis on MRE was considered severe fibrosis. Student’s t-test, Spearman’s r correlation and one-way-ANOVA with FDR correction was applied for statistical analysis.

Results

Serum levels of C4M were elevated in patients with confirmed fibrosis by contrast MRE compared with patients without fibrosis (p = 0.031, AUC: 0.61) (Figure 1A). VICM correlated to the LI score in CD patients (r = 0.26, p = 0.015) and serum VICM levels were elevated in patients with an LI score >2 (p = 0.005, AUC: 0.67) (Figure 1B). VICM was significantly associated with intestinal damage for LI > 20 (LI 0 vs. >20: p = 0.005, AUC: 0.72). PRO-C3 was not associated with intestinal damage or intestinal fibrosis.

Conclusion

Our results indicate that the accumulated intestinal damage and the bowel wall fibrosis in CD are associated with elevated serum levels of VICM and C4M, respectively. Thus, serological biomarkers of basement membrane degradation and inflammation may be a useful tool to monitor intestinal tissue damage and fibrosis development.
P121 Real-world use of the IBD disk tool in unselected cohorts of outpatients
Authors: Sharma N , Savelkoul E , Disney B , Shah A , De Silva S , Pattni S , Iacucci M , Cooney R , Ghosh S
Published: January 2020

Background

The IBD Disability Index (IBD-DI) is a validated health care professional (HCP) administered tool that can assess the functional status of patients in trials. The IBD-Disk was adapted from the IBD-DI as a tool that patients can use to capture their functional status for HCPs to review. We report patient acceptability and use of the IBD-disk in the real-world setting.

Methods

The IBD-Disk was constructed by an expert steering committee of international gastroenterologists/nurses who ranked the IBD-DI items. A modified Delphi process was used to agree on 10 IBD-Disk items. It was administered in outpatient clinics to patients across NHS hospitals. Inclusion criteria comprised patients aged 18 and over, of all ethnicities, with a confirmed diagnosis of IBD. Exclusion criteria were lack of fluency in English, not agreeable to take part or participation was deemed inappropriate. Patients were asked to rate their level of agreement for each item on the IBD Disk on a visual analogue scale of 0–10 (0 = absolutely NO, 10 = definitely YES). We included a difficulty rating of 1–10 to assess ease of completion of the questionnaire (1 = very easy; 10 = very difficult) as well as qualitative feedback.

Results

A total of 377 patients agreed to take part. The mean age of the cohort was 42 years. Two hundred and twenty-one were female (59 %). 287 were White. One hundred and ninety-nine patients had CD, 159 UC, the remaining unknown. Of the domains of the IBD Disk (see Figure), energy levels, sleep and joint pain scored highest (most impairing) with mean values of 5.68, 4.85 and 4.68, respectively, whereas interpersonal interactions and sexual functions were least affected, mean scores 2.51 and 2.81. The mean difficulty rating was 2.3 (SD = 2.29). Correlations were performed between abdominal pain and energy levels/sleep {r = 0.6 and r = 0.56)} and between joint pain and energy levels/sleep {r = 0.57 and r = 0.58). Clinicians highlighted that the IBD-disk opened up conversations beyond GI issues and gave a good overview of well-being. It facilitated discussion on sexual function and body image. Patients’ feedback highlighted that they were glad they were able to express their functional status and its severity.

Conclusion

Energy levels, sleep and joint pain were the most disabling for this unselected IBD cohort. This may help to focus the discussion in the clinic setting. Our experience with the IBD-Disk proved very positive with high patient acceptability.
P124 Clock gene expression levels can differentially distinguish between ulcerative colitis and Crohn’s disease
Authors: Weintraub Y , Cohen S , Chapnik N , Yerushalmy-Feler A , Ben-Tov A , Dotan I , Tauman R , Froy O
Published: January 2020

Background

Pathophysiological mechanisms active in inflammatory bowel disease (IBD), such as mucosal barrier repair, innate and adaptive immune responses, intestinal motility and gut microbiome, all exhibit diurnal variations. Chronic disruption of the molecular clock augments inflammatory response. We have shown that newly diagnosed, naïve to treatment, young IBD patients showed reduced clock gene expression in both inflamed and non-inflamed intestinal tissues and in peripheral White blood cells (WBCs). This reduction correlated with disease activity1. Our aim in the current study was to determine whether certain clock genes correlate with disease activity scores or inflammatory markers in Crohn’s disease (CD) vs. ulcerative colitis (UC).

Methods

Fourteen CD and 11 UC patients, 8–22 years old, were recruited. Patients were evaluated upon diagnosis and during medical treatment. Disease activity scores, C-reactive protein (CRP) and faecal calprotectin (Fcal) levels were measured and WBC were analysed for clock gene (CLOCK, BMAL1, CRY1, CRY2, PER1 and PER2) expression. Clock gene expression levels were correlated to disease activity scores (clinically active vs. remission), CRP levels (<5 mg/l vs. >5 mg/l) and Fcal levels (<250 μg/mg vs. >250 μg/mg) in CD (21 samples) and UC patients (20 samples).

Results

In UC, CLOCK (p < 0.025), CRY1 (p < 0.033) and PER1 (p < 0.038) showed decreased expression when Fcal levels were >>250 μg/mg. When compared with the clinical status only BMAL1 showed reduced expression (p < 0.019). CRP levels showed no correlation with clock gene expression. In CD, CRP as well as the clinical status correlated with clock gene expression. Whereas CLOCK was reduced (p < 0.019), PER2 was induced (p < 0.005) when CRP levels were >5 mg/dl. Furthermore, CLOCK (p < 0.0005), PER1 (0.017) and PER2 (0.044) were reduced in CD patients with an active disease. However, Fcal did not correlate with clock gene expression.

Conclusion

Altered levels of certain clock genes were demonstrated in young CD and UC patients in relapse vs. remission and correlated with Fcal in UC patients and clinical status as well as CRP levels in CD patients.

Reference
P131 The simplified MARIA score is strongly correlated with the MARIA and Clermont scores to analyse the luminal activity of Crohn’s disease (CD) in magnetic resonance and is easier to calculate
Authors: Roblin X , Jardin S , cuilleron M , veyrard P , boschetti G , berger A E , flourie B , nancey S , paul S
Published: January 2020

Background

Two scores have shown their interest in evaluating the luminal activity of CD in magnetic resonance (MR), the MARIA and Clermont scores, but their calculation can be complicated in clinical practice. Recently, the Spanish authors validated a new simplified MARIA score (MARIAs) and retrospectively showed a very good correlation with the initial MARIA score (1). The purpose of this study was to validate this correlation in an independent cohort and to compare its feasibility with other scores.

Methods

This was a retrospective analysis of all MR performed in our department to evaluate the luminal activity of CD. Two independent radiologists each calculated the MARIA, Clermont and MARIAs scores (wall thickness > 3mm, oedema, comb sign, ulcerations), each blind to the other and blind to clinical activity. In case of disagreement between the two radiologists, a third reader analyzed MR activity. Correlations were calculated between these three tests for the entire cohort. In addition, concordance tests were performed for predetermined thresholds of 7 to 11 for the MARIA score, 8.5 to 12.5 for the Clermont score and 1 to 2 for the MARIAs score. The duration of the analysis was reported for each reading. Isolated colonic CD were excluded from the study.

Results

One hundred and twenty-one CD were included (65 in clinical and biological activity, 33% ileal phenotype, mean age: 38.5 years, sex ratio M/F = 54.5%). The agreement between the MARIA score between 7 and 11, the Clermont score between 8.5 and 12.5 and the MARIAs score between 1 and 2 was 0.92 (Fleiss kappa test). The correlation between the MARIA score and its simplified score was very strong (r = 0.93; 95% CI: 0.9–0.95) as well as between the Clermont score and the MARIAs score (r = 0.92 95% CI: 0.89–0.95). Inter-observer agreement was significantly higher in the calculation of the MARIAs score (96%) compared with 80% for the MARIA and Clermont scores (p = 0.04). Reading time was significantly faster for the MARIAs score (3.45 ± 0.4 min) compared with the MARIA (10.05 ± 1.2 min) and Clermont (13.5 ± −3.5 min) scores (p < 0.01). Positive predictive values for deep remission (clinical remission and calprotectin < 250 µg/g stool) were 95% at thresholds <1, <7 and <8.5 for the MARIAs, MARIA and Clermont scores, respectively.

Conclusion

In this independent cohort, we confirm the very strong correlation between the simplified MARIA score and the two reference scores (MARIA and Clermont) in the analysis of MC luminal activity as well as its rapid calculation and strong inter-observer agreement.
P138 Basal plasma cells in normal large bowel: what is normal?
Authors: Castelli P , Abuquteish D , Di Ruscio M , Lunardi G , Zamboni G , Riddell R
Published: January 2020

Background

Basal plasma cells (BPC) are a diagnostic criterion for inflammatory bowel disease (IBD) and their persistence following therapy also indicates an increased risk of relapse. However neither the definition of basal plasma cells nor what is normal has been well established. We examined these parameters and determined whether there is reginal variability throughout the large bowel.

Methods

We looked at two patient populations. Group A) Biopsies from 6 standardised sites around the colon (cecum to rectum) from 37 patients who had normal colonoscopy at IRCCS Sacro Cuore Hospital, Negrar, Verona, Italy for symptoms suggesting irritable bowel syndrome, who were free of all medical therapy. Group B) a validation cohort from Mt Sinai Hospital Toronto using sections from the same 6 sites from 16 subtotal and total colectomy specimens performed for non-obstructing colonic carcinoma, primarily Lynch syndrome. Basal plasma cells were counted between two crypts in both the basal 5%, and the basal 20% of the mucosa. A partitioned visual analogue scale (PVAS) was also developed to see if this could replace counting, especially as the distance between crypts in IBD is variable

Results

In group A, in the lowest 5% part of the lamina propria, basal plasma cells were found throughout the large bowel and were highest in the proximal colon and lowest in the rectosigmoid. The maximum number of plasma cells between crypts was seven for the cecum and two for the rectum, with a gentle gradation between these two. The PVAS (range 1–5) varied from a maximum of 2 proximally to 1 distally. When the basal 20% was counted, the scores ranged from 35 in the cecum to 12 in the rectum, again with a gradation between, but the PVAS increased from a maximum of 3 proximally to 2 in the rectum. In group B the results were virtually to Group A and the PVAS scores were also virtually identical, The main difference was that at least one plasma cell was seen in all sections, likely because tissue sections encompass a much larger area. These results were all statistically significant.

Conclusion

The normal large bowel has a gradation of plasma cells that is highest proximally and lowest distally, however assessed, and needs to be taken into account when assessing the presence of basal plasma cells as an indicator of increased likelihood of relapse of IBD. The PVAS developed can replace the chore of counting, and is likely more meaningful when architectural distortion is present.
P139 Prevalence of infections in patients affected by inflammatory bowel disease treated with anti-TNF-α agents: a single-centre experience
Authors: Imperatore N , Foggia M , Rispo A , Patturelli M , Calabrese G , Testa A , Nardone O , Pellegrini L , Guarino A D , Ricciolino S , Tosone G , Castiglione F
Published: January 2020

Background

Although the efficacy of anti-TNF α agents has dramatically changed the current management of inflammatory bowel disease (IBD), their safety represents an important issue in prescribing anti-TNF. In particular, anti-TNF α treatment has been associated with higher risk of developing infective disease, such as tuberculosis (TBC) and cytomegalovirus (CMV) reactivation and other viral/bacterial diseases. The aim of the present study was to evaluate the incidence and prevalence of CMV, TBC, hepatitis B (HBV) and C (HCV) infection/reactivation and other infections in IBD subjects treated with anti-TNF α.

Methods

retrospective analysis of prospective maintained database including all IBD subjects treated with anti-TNF α (infliximab, adalimumab and golimumab) for at least 1 year in the period 2013–2018, whose infective serological status (Quantiferon TB test, Mantoux, CMV IgM/IgG, HBsAg, HBsAb, HBcAb, HBeAg, HBeAb, anti-HCV, anti-HIV, HSV IgM/IgG, VZV IgM/IgG, EBV IgM/IgG) was known before starting the treatment and during the follow-up. Incidence (number of infections per 100 patient-years) and prevalence of each infection was reported.

Results

Among 689 who started an anti-TNF α agent, 288 subjects (males 52.8%, mean age 28.5 + 12.2 years, Crohn’s disease 82.3%), met inclusion criteria and were enrolled. Total years/patient were 378.08 for infliximab, 627.58 for adalimumab and 8.25 for golimumab. Before starting treatment, CMV IgG antibodies were detectable in the majority (78.8%) of patients, but no case of IgM or CMV-DNA positivity was recorded; three subjects (1%) had latent TBC infection (LTBI) and were treated with isoniazide before starting anti-TNF; one case of HBV and one case of HCV infection were registered. During the anti-TNF α treatment, a total of 58 infective events (20.1%) were recorded: 63.8% during adalimumab and 36.2% during infliximab treatment. The most common infections were: urinary (34.5%), cutaneous (13.8%), HSV (13.8%), HPV (8.6%), upper respiratory infections (8.6%), gastroenteritis (6.9%), pneumonia (5.2%), bacteraemia (3.4%), VZV (3.4%) and de novo CMV (1.7%). Among them, 13 (22.4%) were considered severe, 11 (19%) needed hospitalisation and 9 (15.5%) led to anti-TNF withdrawal. No case of CMV or TBC reactivation was registered during the follow-up. The infection incidence rate was therefore 6.05/100 patient-years for adalimumab and 5.55/100 patient-years for infliximab (p = NS) (Table 1).

Conclusion

IBD patients are at high risk of developing infective disease during anti-TNF α therapy. The recognition of pre-exposure serological status, as well patients’ strict monitoring during maintenance treatment, dramatically reduces the risk of severe reactivation (in particular TBC and CMV reactivation).
P142 Systematic review: patient perceptions of monitoring tools in inflammatory bowel disease
Authors: Goodsall T , Noy R , Nguyen T , Costello S , Jairath V , Bryant R
Published: January 2020

Background

Management of inflammatory bowel disease (IBD) is directed toward both clinical symptoms as well as objective disease activity as a part of a ‘treat to target’ strategy. Despite the increasing burden of disease activity assessment in IBD, patient preferences for monitoring tools have scarcely been considered. This study aimed to describe the available evidence for patient preference, satisfaction, tolerance and/or acceptability of the available monitoring tools in adults with IBD.

Methods

A systematic search of Embase, Medline, Pubmed, Cochrane Central and Clinical Trials.gov from January 1980 to April 2019 was conducted using PRISMA best practice guidelines. Included were all study types reporting on the perspectives of adults with confirmed IBD on monitoring tools, where two or more such tools were compared. Outcome measures with summary and descriptive data were presented.

Results

10 studies evaluating 1846 participants were included. Study size ranged from 18 to 916 participants. Monitoring tools included venepuncture, stool collection and faecal calprotectin (FC), gastrointestinal ultrasound (GIUS), computed tomography (CT), magnetic resonance imaging (MRI), wireless capsule endoscopy (WCE), barium follow-through, and endoscopy. The measurement tools used were visual analogue scales (VAS), Likert scales or binary preference questions. Outcome domains were patient satisfaction, acceptability of monitoring tool, and patient preference. Meta-analysis was not possible due to heterogeneity of data. Overall, patient preference was for non-invasive tools of disease monitoring and these were associated with a higher level of acceptability. Across all included studies, GIUS was identified by patients as the preferred tool for disease activity assessment. Both FC and other forms of imaging (MRE and CTE) were generally considered preferable to endoscopy, however less so than GIUS. Patient preference for blood testing varied, but in one study was lower than endoscopy. Two studies compared VAS acceptability of multiple IBD monitoring tools. Among 1037 patients, GIUS was considered the most acceptable IBD monitoring tool (mean VAS 9.29), as compared with venepuncture (9.28), WCE (8.5), MRE (8.08), stool collection (7.87), colonoscopy (7.07) and sigmoidoscopy (5.27).

Conclusion

This is the first systematic review to evaluate patient perceptions of monitoring tools used in IBD. Patients showed a preference for GIUS and more generally for faecal sampling and non-invasive imaging over endoscopy. Further research should address whether clinician selection of more acceptable monitoring tools in IBD engenders greater patient satisfaction, adherence, and a consequent improvement in disease-related outcomes.
P147 Systematic review: diverting loop ileostomy as treatment option in severe inflammatory bowel disease
Authors: STEENHUIS M , van Son K
Published: January 2020

Background

Severe colitis in the setting of inflammatory bowel disease (IBD), refractory to medical treatment, has traditionally been treated with an emergent colectomy, typically consisting of a two-step approach with a loop diversion in a setting of acute colitis, followed by a colectomy when inflammation has decreased as to minimise the risk of post-operative complications. More recently, several studies have questioned the need for secondary colectomy or have considered stoma reversal a viable option after diversion. We conducted a literature search primarily looking at the incidence of successful reversal or acute colectomy during follow-up. Secondary outcomes were post-surgical complications and clinical improvement after diversion.

Methods

We identified articles using a literature search using six medical databases. Articles were selected on the following criteria; severe colitis (either Crohn’s disease (CD) or ulcerative colitis (UC)), refractory to medical treatment, treated using a temporary loop ileostoma instead of an acute setting colectomy and scoring of clinical improvement parameters, such as decreased medication use and improvement of nutritional state.

Results

Seven studies, of which one was an extension and one was paediatric, were included. All were small studies with 13 to 33 participants, resulting in a total of 145 patients. A range of 16–60% underwent stoma reversal of the diversion based on mucosa and clinical remission with a follow-up rate varying from 4 to 33 months. In six studies, 15–29% of patients undergoing stoma reversal were symptom free during follow-up. Two studies showed partial remission in 55.2% and 69% of participants. Total colectomy in the diverted group, described in 5 studies, was seen in 9–53%. Complication rates ranged from 12–29%. Overall clinical improvement was seen in >80% % of diverted patients. Only 2 studies made subgroup analyses of CD and UC, which showed a better result in CD patients regarding clinical improvement (>90% improvement vs. >80% improvement in UC patients) and rates of successful diversion, which was seen in 3/14 (21%) CD patients and 3/19 (16%) UC patients.

Conclusion

Diverting loop ileostomy in severe IBD is an effective treatment to avoid acute setting colectomy, with improvement in clinical status in >80% of patients and a chance of 15–29% of successful stoma reversal without symptoms of IBD.
P151 Can two different faecal calprotectin assays be used interchangeably in inflammatory bowel disease treatment?
Authors: Van Wassenaer E , Diederen K , Kindermann A , van Leeuwen E M M , D’Haens G R , Benninga M A , Koot B G P
Published: January 2020

Background

Faecal calprotectin (FC) is a broadly used sensitive biomarker for intestinal inflammation in inflammatory bowel disease (IBD) patients. However, in practice, interpretation of results can be complicated due to the use of different assays to determine FC. There is a lack of data comparing different FC assays. This study aimed to assess the agreement between two different assays for determining FC in patients with IBD.

Methods

Between January and April 2017, faecal samples of known IBD patients were tested with two assays: (1) EliA 2 Calprotectin, (Thermo Fisher Scientific Phadia, Sweden) and (2) ELISA tests (EK-Cal, Bühlmann Laboratories, Switzerland). FC measurements >1800 mg/kg were displayed as 1800, as the EK-Cal test could not measure higher values. Samples were not homogenised before testing, and they were tested on the same day. Inter-assay variability was first displayed in a Bland-Altman plot, and then difference in the categorisation of the FC result(1: 0–250 mg/kg, 2: 250–500 mg/kg, 3: >500 mg/kg) was assessed with the linear weighted Kappa (κ). Values for agreement were judged as follows: κ <.0: poor, .0-.20: slight, .21-.40: fair, .41-.60: moderate, .61-.80: substantial, >.80: almost perfect.

Results

A total of 171 patients (mean age 33 years (range: 7–81), 92 (54%) female, 117 (68%) Crohn’s disease, 53 (31%) ulcerative colitis, 1 (1%) IBD-U) were included in this study. Median FC levels were 242 mg/kg (range: 4−1800), and the mean difference between the two assays was 89 mg/kg (range: -1341 – 1140). The mean difference was largest in the high FC category, (3: 200 mg/kg, n = 60), and smallest in the low FC category (1: 5 mg/kg, n = 82)). There was no systematic difference between the two assays (Figure 1). In five out of 171 (3%) patients there was a difference of two categories between the two assays and in 25 out of 171 (15%), there was a difference of one category. There was substantial agreement between the two assays (κ=.78).

Conclusion

There is no systematic difference in FC measurements between the Phadia and EK-Cal assay in this cohort of IBD patients, and agreement between the two is substantial. This suggests that these two assays can be used interchangeably for monitoring IBD patients in clinical practice.