scholarly journals P087 Biomarkers of elastin degradation differentiate between clinically inactive and active disease in ulcerative colitis patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S178-S179
Author(s):  
M Pehrsson ◽  
V Domislović ◽  
M A Karsdal ◽  
M Brinar ◽  
A Barisic ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Disease Severity ◽  
Matrix Protein ◽  
Scoring Systems ◽  
Cathepsin G ◽  
Tissue Remodelling ◽  
Montreal Classification ◽  
Elastin Degradation ◽  
Active Disease

Abstract Background In ulcerative colitis (UC), the state of chronic inflammation results in increased matrix metalloprotease (MMP) and serine protease activity, which effectively leads to a higher degree of intestinal tissue remodelling, including components of the extracellular matrix (ECM). One of these components is elastin a matrix protein of the interstitial matrix in the lamina propria and submucosa, providing tissue resilience and elasticity. As such, we investigated whether elastin degradation in UC patients was associated with disease activity and severity, potentially enabling patient differentiation based on elastin degradation. Methods Twenty-nine UC patients and 29 healthy donors were included in the study. Disease activity was determined according to the partial Mayo score (pMayo >1) and the Mayo Endoscopic Score (MES). Disease severity and extension was assessed using the Montreal classification. Disease severity was additionally assessed using the Trulove and Witt’s (TW) clinical score. The biomarkers of elastin degradation included: MMP-7 (ELM-7) cathepsin-G (EL-CG) and proteinase-3 (ELP-3), measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) correcting for the false discovery rate were applied for the statistical analysis. Results TW: ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison with HD (p < 0.001). Partial Mayo: EL-CG levels in patients with active UC were significantly elevated in comparison with HD (p < 0.01), and UC patients in remission (p < 0.01). ELP-3 levels were likewise significantly elevated in active UC patients compared with HD (p < 0.001), and UC patients in remission (p < 0.01). Montreal classification: ELM-7 was significantly elevated in active UC compared with HD (p < 0.05), and UC patients in remission (p < 0.05). EL-CG were also significantly elevated in active UC compared with HD (p < 0.05), and UC patients in remission (p < 0.05). ELP-3 was significantly elevated in active UC compared with HD (p < 0.01). According to the MES score, ELP-3 levels in moderate-to-severe UC patients were significantly elevated in comparison to HD (p < 0.01). Conclusion The data presented in this study demonstrate an association between biomarkers of proteolytic elastin degradation and disease activity in UC patients especially the protease-3-derived biomarker, ELP-3, showed significant association with active UC in all the clinical scoring systems as well as the MES score. Utilising these minimally invasive elastin degradation biomarkers could serve as surrogate markers for monitoring of disease activity and potentially aid the differentiation of patients with an active disease from patients in remission or with a lower disease activity for UC.

scholarly journals P101 Biomarkers of elastin degradation are associated with clinical and biochemically active disease in Crohn’s disease

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S185-S186
Author(s):  
M Pehrsson ◽  
V Domislović ◽  
M A Karsdal ◽  
M Brinar ◽  
A Barisic ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Activity Index ◽  
Severe Disease ◽  
Matrix Metalloproteases ◽  
Assessment Tools ◽  
Cathepsin G ◽  
Elastin Degradation ◽  
Active Disease

Abstract Background In Crohn’s disease (CD), the extensive and potentially transmural inflammation results in increased activity of both matrix metalloproteases (MMPs) and serine proteases, causing a higher degree of intestinal tissue remodelling. This increased proteolytic activity could potentially cause degradation and loss of function of mechanical and functional matrix proteins, such as elastin. Therefore, we sought to investigate the association between biomarkers of elastin degradation and the disease activity in CD patients. Methods Seventy-two CD patients and 29 healthy donors (HD) were included in the study. Disease activity was determined according to the Crohn’s disease activity index score (CDAI >150) and/or a faecal calprotectin (fCALP >250). Additionally, CD patients were endoscopically assessed according to the simple endoscopic score (SES) for CD. Different protease derived biomarkers of elastin degradation: protease-3 (ELP-3), MMP-7 (ELM-7) and cathepsin-G (EL-CG) was measured in serum by ELISA. One-way ANOVA (Kruskal–Wallis) was applied for the statistical analysis. Results The levels of ELP-3 was significantly elevated in active CD when compared with the HD (p < 0.001), and inactive CD (p < 0.01). Levels of EL-G were significantly elevated when comparing active CD and HD (p < 0.05), with the same result observed for the levels of EL-CG when comparing active CD and the HD (p < 0.05). Endoscopically, ELP-3 was shown significantly elevated in moderate–to-severe CD patients when compared with the HD (p < 0.01). Conclusion In this study, measurements of the elastin degradation markers were capable of differentiating between CD patients with either a clinically active or biochemically active disease, with the biomarker levels being significantly highest in the patients with an active disease. This was also the case when assessing endoscopic disease activity, where the protease-3-derived biomarker levels were highest in patients of moderate-to-severe disease activity. As such, the data provide indications of the beneficial use of these serum biomarkers as additional disease activity assessment tools for CD patients.

scholarly journals Development of Mucosal PNAd+ and MAdCAM-1+ Venules during Disease Course in Ulcerative Colitis

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 891
Author(s):  
Britt Roosenboom ◽  
Ellen G. van Lochem ◽  
Jos Meijer ◽  
Carolijn Smids ◽  
Stefan Nierkens ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
High Endothelial Venules ◽  
Cell Homing ◽  
Colonic Biopsy ◽  
T Cell Homing ◽  
N 93 ◽  
Active Inflammation ◽  
Active Disease

PNAd and MAdCAM-1 addressins on venules are of importance in T-cell homing and potential therapeutic targets in ulcerative colitis (UC). Normally, PNAd+ high endothelial venules (HEVs) are only present in lymphoid organs, whereas small numbers of MAdCAM-1+ venules can be seen in non-lymphoid tissue. We aimed to study their presence in the intestinal mucosa of UC patients at diagnosis and during follow-up, and their correlation with disease activity. Colonic biopsy specimens of 378 UC patients were analyzed by immunohistochemistry for CD3, CD20, ERG, MECA-79 (PNAd) and MECA-376 (MAdCAM-1) and compared to healthy controls (HC). The proportion of PNAd+HEVs in UC at diagnosis was 4.9% (IQR 2.0%–8.3%), while none were detected in HC. During follow-up, PNAd+HEVs completely disappeared in remission (n = 93), whereas the proportion in active disease was similar to baseline (n = 285, p = 0.39). The proportion of MAdCAM-1+venules in UC at baseline was 5.8% (IQR 2.6–10.0). During follow-up, the proportion in remission was comparable to diagnosis, but upregulated (7.5% (IQR 4.4–10.9), p = 0.001) in active disease. In conclusion, PNAd+HEVs appear in UC during active inflammation which could thus serve as a marker for disease activity, whereas MAdCAM-1+venules remain present after inflammation is resolved and increase after subsequent flares, reflecting chronicity and potentially serving as a therapeutic target.

scholarly journals Serum Beta 2-Microglobulin as a Biomarker of Activity in Ulcerative Colitis

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
E H Nashaat ◽  
M M Mohamed ◽  
T M Aziz ◽  
M W Nakhla
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Disease Severity ◽  
Inactive Disease ◽  
Control Group ◽  
Active Ulcerative Colitis ◽  
Presenting Symptoms ◽  
Non Invasive ◽  
Beta 2 ◽  
Beta 2 Microglobulin

Abstract Background ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease that causes inflammation and ulcers in the innermost layers of the large intestine (colon) and rectum. Assessment of intestinal inflammation in UC is crucial and still remains a difficult challenge for the clinician. Although endoscopic modalities with biopsy sampling seem to be the most reliable method for estimating disease severity, they are invasive and costly. Apart from endoscopic interventions, disease severity can be assessed using both laboratory studies and non-invasive imaging tests. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBCs), acid glycoprotein, platelet count and albumin are in common use but have only modest accuracy in reflecting UC disease activity. Therefore, adjunctive use of additional serum markers that will be more sensitive and specific for determination of disease activity and achieving diagnostic accuracy is strongly needed in daily clinical practice. Aim of the Work to investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of ulcerative colitis disease. Patients and Methods a case control study that was conducted at the Gastroenterology Clinic, Internal Medicine Department, Ain Shams University during the period of January to July 2018. 60 patients were recruited for the study. They were divided as follows; Group “A”: 40 patients newly diagnosed as ulcerative colitis based on colonoscopy and biopsy, subdivided as follows; 20 patients with active ulcerative colitis and 20 patients with inactive ulcerative colitis. Group “B”: 20 healthy individuals free from any systemic diseases serving as a control group. Results in this study, the serum levels of serum B2-microglobulins were highest in patients with active ulcerative colitis compared to those with inactive ulcerative colitis and the control groups. Also B2-microglobulins values become higher with higher number of presenting symptoms and endoscopic activity, which becomes higher in severe disease. Conclusion our results revealed that serum B2-microglobulin was simple and non-invasive marker that could be helpful for differentiating active UC from inactive disease. Moreover, it was more helpful when used together with serum laboratory inflammatory indices (ESR and CRP).

scholarly journals Correlation between faecal microbial taxa and ulcerative colitis in different phases of disease activity in a north Indian cohort

2021 ◽  
Author(s):  
garima juyal ◽  
Ajit Sood ◽  
Vandana Midha ◽  
Arshdeep Singh ◽  
Dharmatma Singh ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Phenotypic Variability ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Opportunistic Pathogens ◽  
Differential Abundance ◽  
Mutualistic Association ◽  
Faecal Microbiome ◽  
Active Disease

Objective: A link between gut microbiota and Ulcerative Colitis (UC) has been established in several studies. However, a few studies have examined specific changes in microbiota associated with different phases of disease activity in UC. In this study, we investigated phenotypic variability underlying genetically distinct north Indian (NI) UC patients by identifying differentially abundant taxa between (i) UC patients and healthy controls and (ii) different disease phases of disease activity. Design: 16S rRNA (V3,V4) sequencing of 105 patients with UC [newly diagnosed (n=14); patients in remission (n=36) and active disease (relapse, n=55)]; and 36 healthy controls was performed. The faecal microbiota composition in different phases of UC disease activity and healthy controls was analysed. Results: Lower gut microbial diversity; enrichment of lactate-producing bacteria namely Streptococcus, Bifidobacterium and Lactobacillus; and depletion of butyrate-producing bacteria (e.g., Lachnospiraceae and Ruminococcaceae), was observed among UC patients. Subgroup analysis revealed differential abundance of Escherichia-Shigella, Streptococcus, Enterococcus and Faecalibacterium in newly diagnosed UC patients. No discrete microbial features were observed between patients in remission and those with active disease. Co-occurrence network analysis revealed a mutualistic association between opportunistic pathogens and Bifidobacterium and Lactobacillus and antagonistic relationship with butyrate-producers. Conclusion: This first faecal microbiome study elucidated dysanaerobiosis; loss of short chain fatty acid producers and enrichment of inflammation associated microbes; population specific differential microbial genera; and microbial signature for early dysbiosis, among NI UC cohort.

scholarly journals P141 Scoring endoscopy in pediatric inflammatory bowel disease: a way to improve quality

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S208-S208
Author(s):  
L Norsa ◽  
A Ferrari ◽  
S Arrigo ◽  
M Bramuzzo ◽  
M Deganello Saccomani ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Intraclass Correlation ◽  
Scoring Systems ◽  
Median Number ◽  
Kappa Statistics ◽  
Low Grade ◽  
Inflammatory Bowel

Abstract Background The aim of mucosal healing (MH) as a therapeutic target in paediatric inflammatory bowel diseases (IBD) has emphasised the role of the endoscopy. There is a great variability in evaluating mucosal lesions among different operators, especially in paediatric patients. This multicentre prospective study aims to evaluate the interobserver agreement among paediatric endoscopists in using validated endoscopic scores of IBD in children. Methods Fifteen videos of follow-up ileocolonoscopies in children with IBD (8 ulcerative colitis –UC-, 7 Crohn’s disease –CD-) were selected from 3 different referral sites in Italy. Eleven paediatric endoscopists from different centres were asked to evaluate all videos as independent and blinded readers. The scoring systems used were ulcerative colitis Endoscopic Index of Severity (UCEIS) for UC and simple endoscopic score for Crohn’s disease (SES-CD) for CD. Kappa statistics and intraclass correlation coefficients were used to measure agreement. Furthermore, an experienced adult gastroenterologist evaluated the same videos and scores them. His results were compared with paediatric endoscopists’ findings. Results The median age of the participants was 40 (interquartile range: 6) with a median experience of 12 (14) years in centres with a median number of 140 (230) of paediatric IBDs. Intercluster correlation agreement was 0.298 (95% CI: 0.13–0.55) for UC and 0.266 (0.11–0.52) for CD. When a disease activity categorisation was adopted (remission, moderate, mild and severe) Fleiss’ kappa coefficient was 0.408 (0.29–0.53) for UC and 0.552 (0.43–0.73) for CD (Figure 1). When stratified for item vascular pattern of UC was the most reliable item IC: 0.624 (0.321–0.854). The comparison between paediatric and expert gastroenterologist’s scores is shown in Figure 2. In the multivariate analysis none of the reviewer characteristic affected the readers’ errors. Conclusion This pilot multicentre study shows that there is a low level of agreement among paediatric endoscopists in evaluating children with IBDs. Agreement improved after using a disease activity categorisation, with better results for CD. Regardless to experience, all readers showed a low-grade accordance with adult gastroenterologist. According to these findings, the use of scoring systems should be implemented for all paediatric endoscopists. Future specific training programs should be considered to pursue this goal.

scholarly journals Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn’s disease

2020 ◽  
pp. 205064062097737
Author(s):  
T Manon-Jensen ◽  
S Sun ◽  
M Lindholm ◽  
V Domislović ◽  
P Giuffrida ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Surrogate Marker ◽  
Area Under The Curve ◽  
Inflammatory Bowel ◽  
Active Disease

Background Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn’s disease and ulcerative colitis. Methods We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulfate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn’s disease and 29 ulcerative colitis patients with active and inactive disease was included. Results In the acute and chronic dextran sulfate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn’s disease ( p < 0.05) and ulcerative colitis ( p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve: 0.81, p = 0.0009) and Crohn’s disease (area under the curve: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (Area under the curve: 0.75, p = 0.0219) and Crohn’s disease patients with active disease from those in remission (area under the curve: 0.68, p = 0.05). Conclusion PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn’s disease.

ID: 3526290 ARTIFICIAL INTELLIGENCE (AI) IN ENDOSCOPY - DEEP LEARNING FOR SCORING OF ULCERATIVE COLITIS DISEASE ACTIVITY UNDER MULTIPLE SCORING SYSTEMS

2021 ◽  
Vol 93 (6) ◽  
pp. AB196-AB197
Author(s):  
Michael F. Byrne ◽  
James E. East ◽  
Marietta Iacucci ◽  
Remo Panaccione ◽  
Rakesh Kalapala ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Ulcerative Colitis ◽  
Deep Learning ◽  
Disease Activity ◽  
Scoring Systems
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