scholarly journals New IBD Markers: Definition of Disease Heterogeneity

1995 ◽  
Vol 9 (6) ◽  
pp. 301-304
Author(s):  
Stephan R Targan
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Serum Markers ◽  
Treatment Modalities ◽  
Mucosal Inflammation ◽  
Disease Heterogeneity ◽  
Clinical Phenotypes ◽  
Tnf Α ◽  
Different Types

There is emerging evidence that serum and mucosal markers differentiate Crohn's disease from ulcerative colitis; moreover, subgroups can be defined within each disease. Subgroups have been defined on the basis of genetic, serum and mucosal markers, and are associated with different clinical phenotypes. Antineutrophil cytoplasmic antibodies (ANCA) define subgroups of patients with both ulcerative colitis and Crohn's disease. A new serum marker, 20P-1, has been found in 60 to 70% of patients with Crohn's disease, 20% of ulcerative colitis patients and approximately 10% of the normal control population. The 20P-1 marker further stratifies the subgroups of patients defined by ANCA. In addition to serum markers, genes regulating production of the cytokine tumour necrosis factor (TNF)-α have been shown to be different across ulcerative colitis and Crohn's disease, and within the ulcerative colitis group. Serum markers may reflect differential mucosal inflammatory responses as is best shown by ANCA. B cell clones within the mucosa of 60 to 70% of patients with ulcerative colitis produce ANCA spontaneously. Studies currently underway demonstrate different TNF- α production within the mucosa of patients with Crohn's disease compared with ulcerative colitis patients. Correlation studies with TNF-α microsatellites (genes) are being performed. These markers are the focus of a trial using molecularly engineered products that are capable of inhibiting TNF-α to identify patients likely to respond to anti-TNF therapy. In this constantly evolving climate of understanding and treating inflammatory bowel disease, serum, mucosal and genetic markers as well as genetic associations are being formed to determine clinical phenotypes that may be differentially responsive to very selected treatment modalities. These advances highlight the likelihood that the various markers define different types of mucosal inflammation. The different types of mucosal inflammation will determine the response or resistance to certain types of therapeutic options.

scholarly journals Immunolocalization of leptin and leptin receptor in colorectal mucosa of ulcerative colitis, Crohn’s disease and control subjects with no inflammatory bowel disease

2020 ◽  
Author(s):  
Flavia Merigo ◽  
Alessandro Brandolese ◽  
Sonia Facchin ◽  
Federico Boschi ◽  
Marzia Di Chio ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Lamina Propria ◽  
Leptin Receptor ◽  
Gastrointestinal Symptoms ◽  
Lymphatic Vessels ◽  
Mucosal Inflammation ◽  
Colorectal Mucosa ◽  
Inflammatory Bowel

Abstract The expression of leptin and leptin receptor (Ob-R) has been partially elucidated in colon of patients with inflammatory bowel diseases (IBDs), even though leptin is involved in angiogenesis and inflammation. We previously reported overexpression of GLUT5 fructose transporter, in aberrant clusters of lymphatic vessels in lamina propria of IBD and controls. Here, we examine leptin and Ob-R expression in the same biopsies. Specimens were obtained from patients with ulcerative colitis (UC), Crohn’s disease (CD) and controls who underwent screening for colorectal cancer, follow-up after polypectomy or with a history of lower gastrointestinal symptoms. Immunohistochemistry revealed leptin in apical and basolateral membranes of short epithelial portions, Ob-R on the apical pole of epithelial cells. Leptin and Ob-R were also identified in structures and cells scattered in the lamina propria. In UC, a significant correlation between leptin and Ob-R in the lamina propria was found in all inflamed samples, beyond non-inflamed samples of the proximal tract, while in CD, it was found in inflamed distal samples. Most of the leptin and Ob-R positive areas in the lamina propria were also GLUT5 immunoreactive in inflamed and non-inflamed mucosa. A significant correlation of leptin or Ob-R expression with GLUT5 was observed in the inflamed distal samples from UC. Our findings suggest that there are different sites of leptin and Ob-R expression in large intestine and those in lamina propria do not reflect the status of mucosal inflammation. The co-localization of leptin and/or Ob-R with GLUT5 may indicate concomitance effects in colorectal lamina propria areas.

scholarly journals P302 Diagnostic accuracy of a serum-based biomarker panel for endoscopic activity in ulcerative colitis

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S304-S304
Author(s):  
A HOLMER ◽  
B Boland ◽  
S Singh ◽  
H Le ◽  
J Neill ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Diagnostic Accuracy ◽  
Operating Characteristic ◽  
Mucosal Inflammation ◽  
Serum Samples ◽  
Receiver Operating Characteristic Curves ◽  
Biomarker Panel ◽  
Endoscopic Remission

Abstract Background The endoscopic healing index (EHI, Monitr, Prometheus Biosciences, San Diego, CA) is a serum-based biomarker panel available for identifying mucosal inflammation in Crohn’s disease.[1] We aimed to study its performance for identifying mucosal inflammation in ulcerative colitis. Methods EHI was analysed on serum samples paired with endoscopies from adult patients (≥18 years) participating in a prospective biobank (June 2014 to December 2017). Area under receiver operating characteristic curves (AUROC) were used to assess the accuracy of EHI for endoscopic improvement (EI; Mayo endoscopic sub-score [MES] 0–1) and endoscopic remission (ER; MES 0). Sensitivity for EHI was calculated using a cut-off previously identified for Crohn’s disease which optimised performance for ruling out endoscopic activity (20 points). Alternative cut-offs were explored. Results A total of 114 patients were included, with an overall prevalence of 56% and 44% for EI and ER. The AUROC was 0.79 (95% CI 0.70–0.87) for EI and 0.70 (95% CI 0.61–0.80) for ER. A cut-off of 20 points had a sensitivity of 94% (95% CI 83–99%) for ruling out moderate to severe (MES 2–3) endoscopic activity, and a sensitivity of 84% (95% CI 72–92%) for ruling out mild to severe (MES 1–3) endoscopic activity. A cut off of 40 points or higher had > 90% specificity for ruling in moderate to severe (MES 2–3) or mild to severe (MES 1–3) endoscopic activity. (Table 1) Conclusion EHI has favourable accuracy in identifying the presence of mucosal inflammation in patients with ulcerative colitis. Although it was not developed and validated for ulcerative colitis, further validation is warranted. Reference

scholarly journals Expression of Cytokine-Coding Genes BMP8B, LEFTY1 and INSL5 Could Distinguish between Ulcerative Colitis and Crohn’s Disease

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1477
Author(s):  
Daša Jevšinek Skok ◽  
Nina Hauptman ◽  
Miha Jerala ◽  
Nina Zidar
Keyword(s):  
Gene Expression ◽  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Experimental Validation ◽  
Expression Profiles ◽  
Statistical Significance ◽  
Gene Expression Profiles ◽  
Cytokine Gene Expression ◽  
Treatment Modalities

Ulcerative colitis (UC) and Crohn’s disease (CD) are characterized by an imbalance between pro-inflammatory and anti-inflammatory cytokines, interfering with the resolution of inflammation. Due to the crucial role of cytokines, new insights into their profiles in UC and CD would help to improve our understanding of pathogenesis and enable the development of new treatment modalities. We provide an expression profile of cytokines in UC and CD, using bioinformatics approach, and experimental validation of expression of the selected genes. We retrieved data and analyzed the cytokine gene expression profiles of UC and CD. From ten genes with inverse expression, common to CD and UC, BMP8B, LEFTY1 and INSL5 were selected for gene expression experimental validation. Experimentally, BMP8B and INSL5 were down-regulated in both CD and UC but followed the bioinformatics trend. The expression of genes LEFTY1 and BMP8B was statistically significant when comparing UC and CD in colon and the expression of gene LEFTY1 showed statistical significance when CD in ileum and colon were compared. Using the bioinformatics approach and experimental validation, we found differences in expression profiles between UC and CD for INSL5, LEFTY1 and BMP8B. These three promising candidate genes need to be further explored at different levels, such as DNA methylation and protein expression, to provide more evidence on their potential diagnostic role in CD and UC.

scholarly journals Fulminant Herpes Simplex Hepatitis Secondary to Adalimumab in Crohn’s Disease: A Case Report

2019 ◽  
Vol 12 ◽  
pp. 117954761985897 ◽  
Author(s):  
Kanika Goel ◽  
Mark Bunker ◽  
Anna Balog ◽  
Jan F Silverman
Keyword(s):  
Crohn’S Disease ◽  
Case Report ◽  
Herpes Simplex ◽  
Crohn's Disease ◽  
Rare Case ◽  
Treatment Modalities ◽  
Tnf Α ◽  
Inflammatory Bowel ◽  
Simplex Virus ◽  
Necrosis Factor

Herpes simplex virus (HSV) hepatitis is an uncommon cause of fulminant hepatic failure, seen mostly in immunocompromised patients. Conventional treatment modalities for inflammatory bowel disease (IBD), such as steroids and azathioprine, have been known to cause HSV hepatitis. However, the reported incidence of HSV hepatitis in IBD patients undergoing tumor necrosis factor (TNF)-α inhibitor therapy is very rare. In this case report, we describe a rare case of fulminant HSV hepatitis that developed in a patient with Crohn’s disease after treatment with the TNF-α inhibitor, adalimumab.

scholarly journals Prebiotics in inflammatory bowel diseases

2007 ◽  
Vol 98 (S1) ◽  
pp. S85-S89 ◽  
Author(s):  
Francisco Guarner
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Intestinal Bacteria ◽  
Commensal Bacteria ◽  
Mucosal Inflammation ◽  
Microbial Composition ◽  
Principal Mechanism ◽  
Food Ingredients ◽  
Inflammatory Bowel

In genetically susceptible individuals, an altered mucosal immune response against some commensal bacteria of the gut ecosystem appears to be the principal mechanism leading to intestinal lesions in inflammatory bowel disease (IBD). The information currently available does not provide an exact explanation about the origin of this important dysfunction of the interaction between host and commensal bacteria, but an altered microbial composition has been detected in the gut ecosystem of patients with Crohn's disease or ulcerative colitis. Prebiotics are food ingredients not digested nor absorbed in the upper intestinal tract that are fermented by intestinal bacteria in a selective way promoting changes in the gut ecosystem. Experimental and human studies have shown that inulin and oligofructose stimulate saccharolysis in the colonic lumen and favour the growth of indigenous lactobacilli and bifidobacteria. These effects are associated with reduced mucosal inflammation in animal models of IBD. Strong experimental evidence supports the hypothesis that inulin and oligofructose can offer an opportunity to prevent or mitigate intestinal inflammatory lesions in human Crohn's disease, ulcerative colitis, and pouchitis. Encouraging results have been obtained in preliminary clinical trials.

scholarly journals Immunotherapy of Crohn's disease

1998 ◽  
Vol 7 (3) ◽  
pp. 149-152 ◽  
Author(s):  
C. van Montfrans ◽  
L. Camoglio ◽  
S. J. H. van Deventer
Keyword(s):  
Crohn’S Disease ◽  
T Lymphocytes ◽  
Crohn's Disease ◽  
Experimental Colitis ◽  
Interleukin 10 ◽  
Term Treatment ◽  
Mucosal Inflammation ◽  
Open Label ◽  
Tnf Α ◽  
Long Term Treatment

Although the initiating events of Crohn's disease are unknown, models of experimental colitis have provided new insights in the immunologically mediated pathways of mucosal inflammation. In Crohn's disease activated mucosal T lymphocytes produce proinflammatory cytokines within the mucosal compartment. With this understanding, there has been a shift in past years from the use of unspecific anti-inflammatory agents (corticosteroids, aminosalicylates) to the use of immunomodulatory drugs (azathioprine, methotrexate). Moreover, novel strategies have been designed for specific targets in Crohn's disease, in particular T lymphocytes and cytokines. In an open label study treatment of steroid-refractory Crohn's disease with anti- CD4+ antibodies was well tolerated and showed clinical benefit. However, a sustained depletion of the CD4+ cells precluded further clinical trials. In controlled clinical studies, anti-tumour necrosis factor (TNF-α) antibodies induced com plete remissions and few side effects were observed. One study suggested efficacy in active Crohn's disease of recombinant interleukin-10. Long term treatment studies will have to answer questions about the indications for use, benefit and toxicity. Altogether, these results hold promise for future management of Crohn's disease, where disease-modifying interventions and strategies that effectively maintain disease remission will play a key role.

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