scholarly journals Roles of IL-17A and IL-23 in the Pathogenesis of Ulcerative Colitis and Crohn’s Disease

2021 ◽  
pp. 2526-2535
Author(s):  
Sarah S. Abdul-Hussein ◽  
Ekhlass N. Ali ◽  
Nawal M. F. Alkhalidi ◽  
Neihaya H. Zaki ◽  
Ali H. Ad'hiah
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Family History ◽  
Crohn's Disease ◽  
Smoking Status ◽  
Serum Levels ◽  
Inflammatory Disorder ◽  
Chronic Inflammatory Disorder ◽  
History Of ◽  
Disease Extension

     Inflammatory bowel disease (IBD) is a chronic inflammatory disorder,  the etiology and pathogenesis of which have been suggested to be influenced by cytokines. Two main clinical types of IBD are recognized, namely ulcerative colitis (UC) and Crohn's disease (CD). The present study examined serum levels of two cytokines (IL-17A and IL-23) in 60 IBD patients (30 UC and 30 CD) and 30 healthy controls. The levels were correlated with age, gender, cigarette-smoking status, disease duration, family history, disease extension, symptoms, extra-intestinal manifestations, and medication. The results depicted that IL-17A level was significantly higher in UC and CD patients compared to control (45.2 ± 23.3 and 47.5 ± 34.4 vs. 15.6 ± 7.5 pg/ml, respectively; p < 0.001). Serum level of IL-23 was similarly increased in UC and CD patients compared to control (64.1± 23.7 and 62.5 ± 27.3 vs. 25.2 ± 11.1 pg/ml, respectively). However, the level of both cytokines showed no significant variation between UC and CD patients (p = 0.713 and 0.777, respectively). Distributing UC and CD patients into subgroups according to some characteristics revealed that IL-17A level was significantly increased in UC male compared to female patients (57.3 ± 18.2 vs. 34.5 ± 22.5 pg/ml; p = 0.005). It was also significantly increased in smoker UC patients compared with non-smoker patients (51.9 ± 19.4 vs. 31.6 ± 25.5 pg/ml; p = 0.022). Smoker CD patients also showed a significantly increased level of IL-23 compared to non-smoker patients (72.7 ± 28.5 vs. 52.2 ± 22.6 pg/ml; p = 0.038). In the case of family history, IL-23 level was significantly decreased in UC patients with a family history of IBD compared to CD patients with a family history (84.5 ± 24.3 vs. 50.4 ± 17.0 pg/ml.; p = 0.042). In conclusion, the present data suggest a role for IL-17A and IL-23 in the etiology and pathogenesis of UC and CD.

Inflammatory bowel disease: introduction

2011 ◽  
Author(s):  
R. Mark Beattie ◽  
Anil Dhawan ◽  
John W.L. Puntis
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Family History ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
History Of ◽  
Inflammatory Bowel ◽  
The Uk

Inflammatory bowel disease 288• 25 % of inflammatory bowel disease (IBD) presents in childhood, usually as Crohn's disease or ulcerative colitis. The UK incidence is 5.2/100 000 children <16 years of age. Crohn's disease is the more common. Family history of Crohn's disease or ulcerative colitis is common. Both diseases can occur in the same family....

scholarly journals Differential Effect of Genetic Burden on Disease Phenotypes in Crohn’s Disease and Ulcerative Colitis in a Canadian Cohort

2020 ◽  
Author(s):  
Jack X Q Pang ◽  
Hengameh Kheirkhahrahimabadi ◽  
Sunint Bindra ◽  
Gurmeet Bindra ◽  
Remo Panaccione ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Family History ◽  
Crohn's Disease ◽  
Odds Ratio ◽  
Genetic Risk Score ◽  
Disease Extent ◽  
Age Of Diagnosis ◽  
History Of ◽  
Genetic Burden

Abstract Background and Aims Crohn’s disease (CD) and ulcerative colitis (UC) demonstrate considerable phenotypic heterogeneity and course. Accurate predictors of disease behaviour are lacking. The contribution of genetics and specific polymorphisms is widely appreciated; however, their cumulative effect(s) upon disease behaviour remains poorly understood. Here, we investigate the relationship between genetic burden and disease phenotype in a Canadian inflammatory bowel disease (IBD) Cohort. Methods We retrospectively examined a cohort of CD and UC patients recruited from a single tertiary referral center genotyped using a Goldengate Illumina platform. A genetic risk score (GRS) incorporating strength of association (log odds ratio) and allele dose for 151 IBD-risk loci was calculated and evaluated for phenotypic associations. Results Among CD patients, higher GRS was associated with earlier onset of disease (regression coefficient −2.19, 95% confidence interval [CI] −3.77 to −0.61, P = 0.007), ileal disease (odds ratio [OR] 1.45), stricturing/penetrating disease (OR 1.72), perianal disease (OR 1.57) and bowel resection (OR 1.66). Higher GRS was associated with use of anti-tumor necrosis factor (TNF) (P &lt; 0.05) but not immunomodulators. Interestingly, we could not demonstrate an association between higher GRS and family history of IBD (OR 1.27, P = 0.07). Onset of disease remained statistically significant for never smokers (P = 0.03) but not ever smokers (P = 0.13). For UC, having a higher GRS did not predict the age of diagnosis nor was it predictive of UC disease extent (P = 0.18), the need for surgery (P = 0.74), nor medication use (immunomodulators P = 0.53, anti-TNF P = 0.49). We could not demonstrate an association between increased GRS and having a family history of IBD in the UC group. Conclusions Increasing genetic burden is associated with early age of diagnosis in CD and may be useful in predicting disease behaviour in CD but not UC.

scholarly journals Two for One: Coexisting Ulcerative Colitis and Crohn’s Disease

2002 ◽  
Vol 16 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Grant I Chen ◽  
Fred Saibil ◽  
Izabella Morava-Protzner
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Ulcerative Proctitis ◽  
Crohn’S Colitis ◽  
Crohn's Colitis ◽  
First Case ◽  
History Of

Three cases of coexisting ulcerative colitis and Crohn’s disease are presented. In the first case, the patient had a long-standing history of ulcerative proctitis before developing Crohn’s colitis. In the two remaining cases, the patients presented initially with Crohn’s disease of the ileum and, subsequent to resection, developed ulcerative colitis. Well-documented cases of patients diagnosed with both ulcerative colitis and Crohn’s disease are rare. The literature on such cases is reviewed, and the controversy over whether ulcerative colitis and Crohn’s disease are two distinct diseases is explored.

scholarly journals Pulmonary Crohn's Disease in Down Syndrome: A Link or Linkage Problem

2016 ◽  
Vol 10 (2) ◽  
pp. 206-211
Author(s):  
Danyal Thaver ◽  
Mirza Beg
Keyword(s):  
Down Syndrome ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Pediatric Population ◽  
Pulmonary Nodules ◽  
Pulmonary Involvement ◽  
Lung Nodules ◽  
Inflammatory Disorder ◽  
Ct Guided ◽  
History Of

Crohn’s disease (CD) is an autoimmune inflammatory disorder that primarily affects the gastrointestinal tract. It may have pulmonary involvement, which has been rarely reported in pediatric patients. Down syndrome (DS) has been associated with increased frequency of autoimmune diseases. However, associations between CD and DS have been rarely reported. We present the case of a 5-year-old girl with known DS and a history of chronic intermittent abdominal pain who presented with persistent pneumonia. Her workup included a chest computed tomography (CT) scan that showed multiple noncalcified pulmonary nodules. An extensive infectious workup was done that was negative. CT-guided needle biopsy of the lung nodules showed necrotizing granulomas. This raised concern for primary CD with extraintestinal pulmonary manifestation. An esophagogastroduodenoscopy and colonoscopy were performed, and colon biopsies showed scattered epithelioid granulomas. Based on this information, there was consensus that her lung nodules were secondary to CD. She was started on standard therapy for CD, and her abdominal and respiratory symptoms gradually improved. However, she continues to have mild residual lung calcification and fibrosis. To our knowledge, this is the first reported case of pulmonary CD in a child with DS. The natural history of pulmonary CD in the pediatric population is not very well studied. Furthermore, since DS has been well known to be associated with increased frequency of malignancies and autoimmune conditions due to immune dysregulation, it is difficult to predict the severity and possible complications in this patient.

scholarly journals Crohn’s disease severity in familial and sporadic cases

Gut ◽  
1999 ◽  
Vol 44 (1) ◽  
pp. 91-95 ◽  
Author(s):  
F Carbonnel ◽  
G Macaigne ◽  
L Beaugerie ◽  
J P Gendre ◽  
J Cosnes
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Family History ◽  
Crohn's Disease ◽  
Disease Severity ◽  
Bowel Disease ◽  
History Of ◽  
Sporadic Cases ◽  
Inflammatory Bowel ◽  
Excisional Surgery

BackgroundHaving a relative with inflammatory bowel disease increases the risk for Crohn’s disease but may also increase its severity in affected patients.AimsTo evaluate the influence of a family history on Crohn’s disease course and severity.Methods1316 patients followed in the same unit were studied retrospectively. Age at onset, duration of illness, site, and extent of disease were determined in patients with and without a family history. Additionally, disease severity was estimated by the need for medical therapy (steroid and immunosuppressive requirement) and the frequency and extent of excisional surgery.Results152 (12%) patients had a family history of inflammatory bowel disease. Duration of follow up was longer in patients with a family history and there were more operations for perforating complications in familial cases. However, the importance of medical therapy, and the incidence and extent of excisional surgery were similar in familial and and sporadic cases. Kaplan-Meier estimated time to prescription of immunosuppressive drugs and first intestinal resection were similar in familial and sporadic cases. When the 152 patients with familial Crohn’s disease were paired for sex, location of disease at onset, date of birth, and date of diagnosis with 152 patients with sporadic Crohn’s disease, the disease severity remained similar in the two groups of paired patients.ConclusionPatients with Crohn’s disease and a family history of inflammatory bowel disease do not have a more severe course.

1105 Serum gASCA, Anti-L and Smoking Status Are Associated with Crohn's Disease-Like Phenotype After Pelvic Pouch Surgery for Ulcerative Colitis

2009 ◽  
Vol 136 (5) ◽  
pp. A-171
Author(s):  
Diane Verbeeten ◽  
Raquel Milgrom ◽  
Wei Xu ◽  
Joanne M. Stempak ◽  
A. Hillary Steinhart ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Smoking Status ◽  
Pelvic Pouch ◽  
Pouch Surgery ◽  
Pelvic Pouch Surgery

scholarly journals Natural History of  Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study

2020 ◽  
Author(s):  
Basavaraj Kerur ◽  
Eric I Benchimol ◽  
Karoline Fiedler ◽  
Marisa Stahl ◽  
Jeffrey Hyams ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Bowel Surgery ◽  
Age Of Diagnosis ◽  
History Of ◽  
Inflammatory Bowel

Abstract Background The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. Methods We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. Results The study population included 269 children (105 [39%] Crohn’s disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9–5.2). Most (94%) Crohn’s disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn’s disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Conclusions Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%–15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.

scholarly journals Profiling Non-Coding RNA Levels With Clinical Classifiers in Pediatric Crohn’s Disease

2020 ◽  
Author(s):  
Ranjit S. Pelia ◽  
Suresh Venkateswaran ◽  
Jason D. Matthews ◽  
Yael Haberman ◽  
David J. Cutler ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Disease Progression ◽  
Protein Function ◽  
Inflammatory Disorder ◽  
Substantial Impact ◽  
Chronic Inflammatory Disorder ◽  
Inflammatory Status ◽  
Disease Behavior ◽  
Non Coding Rnas

Abstract Background: Crohn’s disease (CD) is a heritable chronic inflammatory disorder. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation by affecting gene expression, but can also directly affect protein function, thus having a substantial impact on biological processes. We investigated whether non-coding RNAs (ncRNA) at diagnosis are dysregulated during CD at different CD locations and future disease behaviors to determine if ncRNA signatures can serve as an index to outcomes. Methods: Using subjects belonging to the RISK cohort, we analyzed ncRNA from the ileal biopsies of 345 CD and 71 non-IBD controls, and ncRNA from rectal biopsies of 329 CD and 61 non-IBD controls. Sequence alignment was done (STAR package) using Human Genome version 38 (hg38) as reference panel. The differential expression (DE) analysis was performed with EdgeR package and DE ncRNAs were identified with a threshold of fold change (FC) >2 and FDR < 0.05 after multiple test corrections. Results: In total, we identified 130 CD specific DE ncRNAs (89 in ileum and 41 in rectum) when compared to non-IBD controls. Similarly, 35 DE ncRNAs were identified between B1 and B2 in ileum, whereas no differences among CD disease behaviors were noticed in rectum. We also found inflammation specific ncRNAs between inflamed and non-inflamed groups in ileal biopsies. Overall, we observed that expression of mir1244-2, mir1244-3, mir1244-4, and RN7SL2 were increased during CD, regardless of disease behavior, location, or inflammatory status. Lastly, we tested ncRNA expression at baseline as potential tool to predict the disease status, disease behaviors and disease inflammation at 3-year follow up.Conclusions: We have identified ncRNAs that are specific to disease location, disease behavior, and disease inflammation in CD. Both ileal and rectal specific ncRNA are changing over the course of CD, specifically during the disease progression in the intestinal mucosa. Collectively, our findings show changes in ncRNA during CD and may have a clinical utility in early identification and characterization of disease progression.

scholarly journals Mucosal Healing in Crohn’s Disease: Bull’s Eye or Bust? “The Pro Position”

2021 ◽  
pp. 1-6
Author(s):  
Neil O’Moráin ◽  
Jayne Doherty ◽  
Roisin Stack ◽  
Glen A. Doherty
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mucosal Injury ◽  
Mucosal Healing ◽  
Inflammatory Disorder ◽  
Stricture Formation ◽  
Chronic Inflammatory Disorder ◽  
Non Invasive ◽  
Appropriate Treatment ◽  
Bull's Eye

<b><i>Background:</i></b> Crohn’s disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. <b><i>Summary:</i></b> Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. <b><i>Key Messages:</i></b> Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.

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