bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt;2 in UC and a Harvey–Bradshaw &lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &gt; 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

Abstract

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 (&lt;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

Abstract

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 &gt;/= 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 &gt;2 (p = 0.005, AUC: 0.67) (Figure 1B). VICM was significantly associated with intestinal damage for LI &gt; 20 (LI 0 vs. &gt;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

Abstract

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

Abstract

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 (&lt;5 mg/l vs. &gt;5 mg/l) and Fcal levels (&lt;250 μg/mg vs. &gt;250 μg/mg) in CD (21 samples) and UC patients (20 samples).

Results
In UC, CLOCK (p &lt; 0.025), CRY1 (p &lt; 0.033) and PER1 (p &lt; 0.038) showed decreased expression when Fcal levels were &gt;&gt;250 μg/mg. When compared with the clinical status only BMAL1 showed reduced expression (p &lt; 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 &lt; 0.019), PER2 was induced (p &lt; 0.005) when CRP levels were &gt;5 mg/dl. Furthermore, CLOCK (p &lt; 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