scholarly journals ZBTB6 is hyper-methylated and differentially expressed in the blood of patients with Crohn’s disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
The United States ◽  
Differentially Expressed ◽  
Economic Productivity ◽  
Unbiased Manner ◽  
Inflammatory Bowel ◽  
Disease Analysis ◽  
Broad Complex

Crohn’s disease, an inflammatory bowel disease of the gastrointestinal tract (1), causes significant morbidity and nearly 3.5 billion dollars in lost economic productivity in the United States (2) due to complications of the disease. We mined transcriptome and methylome datasets (3, 4) to understand, in an unbiased manner, the most significant changes in gene expression and DNA methylation in the hematopoietic system of patients with Crohn’s disease (CD). We identified the zinc finger and BTB (broad complex, tramtrack, bric-à-brac) domain-containing gene ZBTB6 (5, 6) as one of the most differentially expressed genes in the whole blood of patients with Crohn’s disease. Analysis of a separate data revealed that the ZBTB6 locus was one of the most differentially methylated sites globally in the blood of patients with Crohn’s disease when compared to the blood of healthy patients. ZBTB6 is differentially methylated and differentially expressed in the blood of patients with Crohn’s disease, and more significantly so than the vast majority of the human genome. These data point to inhibition of ZBTB6 gene expression by hyper-methylation of the ZBTB6 locus and suggest that titration of some function or transcriptional target of ZBTB6 may be an important event in the pathogenesis of Crohn’s disease.

scholarly journals The gene encoding the B-cell activating factor and B-lymphocyte stimulator (BAFF/BLyS), TNFSF13B, is differentially expressed in the blood of patients with Crohn’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
B Lymphocyte ◽  
Differentially Expressed ◽  
Gene Encoding ◽  
B Cell Activating Factor ◽  
Bowel Diseases ◽  
B Lymphocyte Stimulator ◽  
Inflammatory Bowel ◽  
Disease Analysis

Inflammatory bowel diseases (IBD) include Crohn’s Disease and Ulcerative Colitis (1). We mined published microarray data to understand how gene expression in the hematopoietic compartment of patients with Crohn’s Disease is most different from that of healthy controls (2-4). Across two datasets (2, 3), we found that BAFF, also known as the B-lymphocyte stimulator (BLyS), encoded by the gene TNFSF13B (5), was differentially expressed in the blood of patients with Crohn’s Disease . Analysis of a third dataset (4) revealed that BAFF was among the genes most differentially expressed in monocyte-derived macrophages from patients with Crohn’s Disease. Serum BAFF, fecal BAFF, and BAFF expression in the intestinal mucosa has been demonstrated to be increased in patients with IBD (6, 7). We show here that expression of BAFF in the peripheral blood of patients with Crohn’s Disease is also increased.

scholarly journals 2′-5′-oligoadenylate synthetase 2 (OAS2) is differentially expressed in the blood of patients with Crohn’s disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Treatment Options ◽  
Gastrointestinal Disorder ◽  
The United States ◽  
Differentially Expressed ◽  
Inflammatory Disorder ◽  
Oligoadenylate Synthetase ◽  
Public Datasets

Crohn’s disease, a complex genetic inflammatory disorder of the gastrointestinal tract (1), has a prevalence of 214 per 100,000 in the United States (2), one of the highest in the world. Understanding of the interaction between genetic susceptibility loci (1) and triggers from the environment (3, 4) is growing but there are still no curative treatments for patients with Crohn’s disease (CD); some patients will fail even the most advanced treatment options (5). Though CD is considered a gastrointestinal disorder, hematologic disturbances are found in patients with Crohn’s disease and anemia is the most common extra-intestinal manifestation of Crohn’s disease (6). To understand the most significant gene expression changes in the hematologic system of patients with Crohn’s disease, we mined published and public datasets (7, 8) containing transcriptome data from the monocyte-derived macrophage (MDM) and multiplexed gene expression data from the regulatory T-cells (Treg) of patients with Crohn’s disease. We found that interferon-inducible nucleic acid sensor 2′-5′-oligoadenylate synthetase 2 (OAS2) (9) was among the most differentially expressed genes in both MDM and Treg from patients with Crohn’s disease. OAS2 expression was significantly lower in MDM and Treg from patients with Crohn’s disease compared to healthy controls. These data reveal compromised expression of an antiviral dsRNA sensor in the blood of patients with Crohn’s disease.

scholarly journals DOP22 Integrative -omic analysis reveals microbiota mediated molecular mechanisms influencing host mucosal gene expression in Crohn’s Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S061-S062
Author(s):  
P Sudhakar ◽  
T Andrighetti ◽  
S Verstockt ◽  
C Caenepeel ◽  
M Ferrante ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Molecular Mechanisms ◽  
Bacterial Species ◽  
Differentially Expressed ◽  
Mucosal Barrier ◽  
Bacterial Proteins ◽  
The Impact ◽  
Hub Proteins

Abstract Background Mechanistic evidence linking gut microbial changes and host mucosal barrier responses in patients with Crohn’s disease (CD) is lacking. In this study, we used a computational approach to integrate gut microbial and intestinal gene expression in CD patients. Methods Bacterial species, bacterial genes/transcripts with enhanced abundances/transcriptional activity in CD (t-statistic of > 2 and Q-value < 0.05), as well as mucosal (ileum/rectum) differentially expressed genes (DEGs) between CD (n =43) and non-IBD (n=22) subjects were retrieved from the Inflammatory Bowel Disease Meta -Omics Database (IBDMDB). The impact of bacterial proteins on host gene expression was inferred using MicrobioLink, a computational tool for inferring microbe-host interactions. Drug target information was retrieved from OpenTargets. Paired 16S read-outs from stool samples and gene expression data from ileal biopsies in CD patients (n=20) and non-IBD controls (n=15), cross-sectionally collected at our IBD referral center, were used for independent validation. Results Across the 8 identified bacterial species enriched in CD, 3.7% (n= 743) of the orthologous groups were identified as being able to bind to human proteins. Network diffusion analysis uncovered bacterial proteins which could cumulatively modulate the expression of 42% of the genes differentially expressed in the ileum of CD patients. Topological and pathway analysis of the inferred signaling network modulated by the microbiota revealed several key hub proteins and immune-related pathways associated with IL-4, IL-2 and IL-13 signaling, receptor tyrosine-kinases, NFkB, and toll-like receptors including TLR4. Seventy-eight percent of the DEGs in our discovery cohort were also differentially expressed in the validation cohort (R2 = 0.907). Bacterial proteins post-translationally modifying host receptors resulted in the up-regulation of several pro-inflammatory cytokines via critical hub proteins such as NFkB (Figure 1). We observed different levels of locational specificity (from 35 to 61%) for the top regulators such as SPI1, STAT1 and NFKB1in terms of genes regulated by them in ileum and rectum. 24 proteins including ITGA4 and JAK1 from the ileal and rectal signaling networks are existing targets of CD drugs such as vedolizumab and tofacitinib, filgotinib and upadacitinib respectively. Conclusion Our findings outline the potential mechanisms of microbiome-induced host responses and provide insights into designing microbiome-mediated therapies to prevent and/or treat CD.

P125 COMPLICATIONS FOLLOWING OUTPATIENT COLONOSCOPY IN INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S24-S24
Author(s):  
Daniel Chu ◽  
Po-Hung Chen ◽  
Steven Brant ◽  
Steven Miller ◽  
Natasha Turner ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
General Population ◽  
Bowel Disease ◽  
Intestinal Perforation ◽  
The United States ◽  
Icd 10 ◽  
Inflammatory Bowel

Abstract Inflammatory Bowel Disease (IBD) patients have frequent complications after surgical procedures. Inflammation, immunosuppression and other factors that are more common in Crohn’s disease (CD) and ulcerative colitis (UC) may play a role in increasing their complication risk profile. IBD patients also undergo colonoscopy procedures more frequently than the general population. We aimed to identify risks of complications during or within 7 days of colonoscopy in IBD patients. Methods: Colonoscopy procedures performed between January 2016 through March 2019 in an outpatient setting (hospital or ambulatory surgical center) were identified from the United States Medicare fee-for-service claims. All Medicare beneficiaries were eligible. Colonoscopy was identified using the Healthcare Common Procedure Coding System (HCPCS) codes (‘45378’ through ‘45393’ and ‘45398’). A patient was considered to have Crohn’s disease (CD) if ICD-10-CM code K50.x was recorded; Ulcerative Colitis (UC) if ICD-10-CM code K51.x was recorded; and IBD if either was recorded on the date of the procedure. Complications recorded during the procedure included intestinal perforation (K63.1), gastrointestinal hemorrhage (K92.2), and “other post-procedural complications of the digestive system” (K91), including, but not limited to, post-gastrectomy syndrome, malabsorption, and intestinal obstruction. We examined these complications in procedures performed on IBD patients compared to the general population using logistic regression. We accounted for age, sex, race, year of colonoscopy, comorbidity score, and procedure discontinuation (identified by HCPCS modifier) in the analysis. A random effect for patient was included in the model to account for multiple procedures performed in the same patient during the study period, restricting patients from contributing multiple procedures. Results: There were 3,181,759 eligible procedures. There were 26,583 (0.84%) colonoscopy procedures in CD patients and 50,708 (1.59%) in UC patients. After accounting for other risk factors, CD and UC were more likely to have intestinal perforation than the non-IBD population (CD OR=2.7, 95% CI: 1.1–6.5; UC=OR 1.9, 95% CI 0.9–4.1), with CD having a statistically significant increase. Women were at greater risk for perforations (OR=1.3; 95% CI: 1.0–1.7). Conversely, IBD patients were less likely than non-IBD patients to have a complication recorded as “other” (CD OR=0.5; 95% CI: 0.2–0.9; UC OR=0.5; 95% CI:0.3–0.8). Older age at colonoscopy (OR=1.02, 95% CI 1.01–1.03), six or more comorbidities (OR=1.9, 95% CI: 1.5–2.3) and procedure discontinuation (OR=2.0, 95% CI 1.2–3.4) were associated with complications regardless of IBD status. Conclusion: IBD was associated with higher risk of perforation, and lower risk of other postprocedural complications in outpatient colonoscopy procedures.

scholarly journals Exercise and Crohn’s Disease: Speculations on Potential Benefits

2006 ◽  
Vol 20 (10) ◽  
pp. 657-660 ◽  
Author(s):  
Victor Ng ◽  
Wanda Millard ◽  
Constance Lebrun ◽  
John Howard
Keyword(s):  
Physical Activity ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gastrointestinal Symptoms ◽  
The United States ◽  
Chronic Inflammatory Bowel Disease ◽  
Potential Benefits ◽  
Patient Groups ◽  
Inflammatory Bowel ◽  
Low Intensity Exercise

Crohn’s disease (CD) is a chronic inflammatory bowel disease that affects nearly one million people in the United States and Canada. While current pharmaceutical treatments are effective in controlling symptoms, patients continue to experience a reduced quality of life (QOL). Based on preliminary studies, QOL in CD patients may be improved by engaging in physical activity. Exercise may decrease CD activity and reduce psychological stress. Current research also suggests that low-intensity exercise does not exacerbate gastrointestinal symptoms and does not lead to flare-ups. Furthermore, exercise appears to reduce CD symptoms and improve QOL. In summary, physical activity may be beneficial to certain patient groups, but more studies are needed before broad recommendations can be made.

Inflammatory Bowel Disease in the United States from 1998 to 2005: Has Infliximab Affected Surgical Rates?

2009 ◽  
Vol 75 (10) ◽  
pp. 976-980 ◽  
Author(s):  
Rebecca R. Cannom ◽  
Andreas M. Kaiser ◽  
Glenn T. Ault ◽  
Robert W. Beart ◽  
David A. Etzioni
Keyword(s):  
United States ◽  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Surgical Care ◽  
The United States ◽  
Population Based ◽  
Inflammatory Bowel

The treatment costs for patients in the United States with inflammatory bowel disease (IBD) exceed 1.7 billion dollars/year. Infliximab, an antibody to tumor necrosis factor-α, has been extensively used to treat IBD, with 390,000 IBD patients receiving the drug since its FDA approval in 1998. We sought to determine the impact of infliximab on population-based rates of hospitalizations and surgical care for patients with IBD in the United States. We used data from the Nationwide Inpatient Sample to analyze patterns of hospital-based treatment provided to patients with IBD between 1998 and 2005. Data from this analysis were combined with census data to calculate trends in population-based rates of treatment. Overall rates of hospitalization for patients with Crohn's disease and ulcerative colitis increased significantly between 1998 and 2005 (5.1%/year and 3.4%/year respectively, P < 0.001 for each). During the same time period there were no changes in the overall rates of surgical care. The expanding use of infliximab has not significantly impacted the use of surgical procedures for patients with either ulcerative colitis or Crohn's disease, and rates of nonsurgical hospitalizations have actually increased. Even in the era of infliximab, surgical care remains a mainstay in the treatment of IBD.

scholarly journals Glucocorticosteroids in the treatment of inflammatory bowel disease and approaches to minimizing systemic activity

2013 ◽  
Vol 6 (2) ◽  
pp. 137-156 ◽  
Author(s):  
Cosimo Prantera ◽  
Stefano Marconi
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
The United States ◽  
Prolonged Treatment ◽  
Medline Search ◽  
Inflammatory Conditions ◽  
Number Of Patients ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Maintenance Of Remission

Inflammatory bowel diseases (IBDs) are a group of inflammatory conditions characterized by chronic, uncontrolled inflammation of the gastrointestinal tract. Reported prevalence is high in the United States and northern Europe, while the incidence varies greatly across the rest of Europe. Glucocorticosteroids are the standard treatment for IBD, but due to adverse events their use can be limited. However, new formulations of glucocorticosteroids have been developed to reduce systemic activation. The aim of this review was to assess and summarize the efficacy and safety of new formulations of glucocorticosteroids. A MEDLINE search identified publications focused on new formulations of nonsystemic steroid-based drugs for IBD and benefits and limitations of each of the new glucocorticosteroid formulations were identified. Budesonide has good efficacy and is an established treatment for Crohn’s disease; it has been shown to be beneficial for the induction of remission in these patients, although it is not recommended for the maintenance of induced remission. Glucocorticosteroids are not recommended for the maintenance of remission in patients with IBD. However, a recent study suggested that beclomethasone dipropionate may be effective for prolonged treatment in patients in the postacute phase of Crohn’s disease who were treated with a short course of systemic steroids. The efficacy of fluticasone propionate and prednisolone metasulphobenzoate in IBD is not well established given the small number of patients enrolled in the few published clinical trials. While the tolerability of these glucocorticosteroids is favourable, more research comparing these new agents with traditional systemic glucocorticosteroids is warranted.

scholarly journals IFITM1 is differentially expressed in the blood of patients with Crohn’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Regulatory T Cells ◽  
Whole Blood ◽  
Differentially Expressed Gene ◽  
Differentially Expressed ◽  
Interferon Signaling ◽  
Oligoadenylate Synthetase

The interferon pathway (1) is an innate immune signaling system that evolved to protect multicellular organisms from viral infections (2). The expression of multiple gene families is expressed following activation of interferon signaling (1); one of these is the antiviral interferon inducible transmembrane proteins, or IFITM gene family (3). Using publicly available datasets (4, 5), we identified the interferon induced transmembrane protein 1, IFITM1 (6-10), as a differentially expressed gene in the whole blood and CD4+ CD25+ regulatory T-cells of patients with Crohn’s Disease. IFITM1 was expressed at significantly higher levels in the whole blood and Treg of patients with Crohn's Disease than in non-affected control subjects. We previously reported that changes in gene expression of the double stranded ribonucleic acid sensor, 2’-5’-oligoadenylate synthetase, OAS2, were among the most significant quantitive differences in the gene expression of monocyte-derived macrophage and regulatory T-cells from patients with Crohn’s Disease when compared to those not affected. Together, these data suggest that a primary defect in the coordination of the host response to viral infection in the hematopoietic compartment, through nucleic acid sensing and subsequent interferon signaling may be fundamentally linked with the pathogenesis of Crohn’s Disease.

scholarly journals CARD16 is differentially expressed in the blood of patients with Crohn’s Disease.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Monozygotic Twins ◽  
Muramyl Dipeptide ◽  
Differentially Expressed ◽  
Peripheral Blood Mononuclear ◽  
Disease Etiology ◽  
Economic Productivity

Crohn’s Disease (CD) is an inflammatory bowel disease that causes significant morbidity, declines in quality of life and loss of economic productivity (1, 2). Twin studies show concordance rates at 58.3% and 63.3% in monozygotic twins demonstrating that genetic factors contribute to the disease etiology in a significant manner (3, 4). We mined a published microarray dataset to perform global differential gene expression profiling using the blood of patients with Crohn’s Disease (5). We identified the caspase recruitment domain family member 16, CARD16, also known as COP and Pseudo-ICE as among the most differentially expressed genes in the blood of patients with Crohn’s Disease. CARD16 expression in the whole blood of patients with Crohn’s Disease was significantly higher than in the blood of healthy, non-affected subjects. Analysis of a separate dataset (6) revealed that CARD16 is a transcriptionally activated in peripheral blood mononuclear cells following stimulation with muramyl dipeptide. CARD16 has been described as both a negative and positive regulator of interleukin-1 𝛃 (IL-1 𝛃) secretion (7, 8) and an activator of NF-kB signaling (9). These data suggest that differential and significantly increased expression of CARD16 in the blood of patients with Crohn’s Disease, in conjunction with the contrasting roles of CARD16 in inflammasome versus NF-kB signaling might contribute to the dysregulated cytokine profile seen in the hematopoietic tissues of patients with Crohn’s Disease (10-15).

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