scholarly journals Genotype–phenotype associations of polymorphisms within the gene locus of NOD-like receptor pyrin domain containing 3 in Swiss inflammatory bowel disease patients

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Priyatharsan Yoganathan ◽  
Jean-Benoit Rossel ◽  
Sebastian Bruno Ulrich Jordi ◽  
Yannick Franc ◽  
Luc Biedermann ◽  
...  

Abstract Background Genetic variations within the regulatory region of the gene encoding NOD-like receptor pyrin domain containing 3 (NLRP3) have been associated with Crohn’s Disease (CD). NLRP3 is part of the NLRP3-inflammasome that mediates the maturation of IL-1β and IL-18. Carrying the major allele of the single nucleotide polymorphisms (SNPs) rs10733113, rs4353135 and rs55646866 is associated with an increased risk for CD. We here studied the impact of these polymorphisms on clinical characteristics in patients of the Swiss IBD Cohort Study (SIBDCS). Methods We included 981 Crohn’s disease (CD) patients and 690 ulcerative colitis (UC) patients of the SIBDCS. We analyzed whether three CD-associated NLRP3 polymorphisms have an impact on the clinical disease course in these patients. Results In CD patients presence of the major allele (G) of rs10733113 was associated with less surgeries and lower maximal CDAI and a similar trend was observed for rs55646866 and rs4353135. Presence of the major allele of all three SNPs was negatively correlated to maximal CDAI. In UC patients homozygous genotype for the major allele (CC) for rs55646866 was associated with a higher age at diagnosis and a higher MTWAI index. Homozygous genotype for the major allele of all three polymorphisms was associated with a higher number of ambulatory visits and longer hospital stays. Conclusions In CD patients presence of the major allele of all three polymorphisms was associated with markers of a less severe disease course, while in UC the homozygous genotype for all major alleles suggested a more severe disease activity.

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S012-S012
Author(s):  
M D Wewer ◽  
M Zhao ◽  
A Nordholm-Carstensen ◽  
J B Seidelin ◽  
J Burisch

Abstract Background Perianal Crohn’s disease (pCD) has a major negative impact on patients’ quality of life and is complex to treat. Despite its putative high frequency and burden for patients, only a few studies have investigated the incidence, disease course and associated cancer-risk in a population-based setting. The aim was to assess the incidence and course of pCD in adult patients with CD within a 19-year period. Specifically, describing changes in medical and surgical management as well as rates of cancer. Methods The cohort comprised all individuals >18 years diagnosed with CD in Denmark between 1 January 1997 and 31 December 2015. Patients were identified in the National Patient Registry. Chi-square test, Mann–Whitney–Wilcoxon test and multivariate Cox regression analysis were used. Results A total of 1,697/9,739 (17%) patients with CD were found to have pCD. Perianal fistulas were the most common manifestation accounting for 943 (56%) cases. The onset of pCD before CD diagnosis occurred in 32%. The overall incidence of pCD was 20/1,000 patient-years. The incidence of pCD remained stable over time. More patients with pCD were treated with immunomodulators (70%) and biologics (35%) than those without pCD (51%, p < 0.001 and 15%, p < 0.001, respectively). Defunctioning stoma was performed in 157/943 (17%) of perianal fistula patients. Stoma formation in relation to resection was performed in 112/943 (12%) of perianal fistula patients. Patients with pCD were found to have a significantly increased risk of undergoing major abdominal surgery compared with patients without pCD (hazard ratio: 1.52, 95% CI: 1.40 to 1.65, p < 0.001). The incidence rate ratios of anal and rectal cancer in pCD patients were 12.46 (95% CI: 5.07 to 30.59, p < 0.001) and 2.41 (95% CI: 1.31 to 4.42, p = 0.003) respectively, when compared with non-IBD matched controls. The incidence rate ratio of anal and rectal cancer in pCD patients was 2.36 (95% CI: 0.86 to 6.50, p = 0.09) and 1.35 (95% CI: 0.68 to 2.68, p = 0.38) respectively, when compared with CD patients without pCD. Conclusion In this nationwide study, 17% of the CD patients developed pCD. The continuing high incidence of pCD suggests a limited disease-modifying effect of biologics. Patients with pCD were at increased risk of undergoing major surgery compared with non-pCD patients. The risk of rectal or anal cancer was increased in patients with pCD compared with non-IBD matched controls. These findings encourage surveillance of rectal and anal cancer.


Author(s):  
M D Wewer ◽  
M Zhao ◽  
A Nordholm-Carstensen ◽  
P Weimers ◽  
J B Seidelin ◽  
...  

Abstract Background and Aims Perianal Crohn’s disease [CD] places a considerable burden on patients’ quality of life and is complex to treat. Despite its impact and high frequency, few studies have investigated the incidence and disease course of perianal CD. The aim of this study was to assess the incidence and disease course of perianal CD in adult patients throughout a 19-year period. Methods The cohort comprised all individuals aged 18 years or older who were diagnosed with CD in Denmark between January 1, 1997, and December 31, 2015, according to the National Patient Registry [NPR]. Results A total of 1812 [19%] out of 9739 patients with CD were found to have perianal CD. Perianal fistulas were the most common manifestation, accounting for 943 [52%] cases. The incidence of perianal CD remained stable over time. Patients with perianal CD were found to have an increased risk of undergoing major abdominal surgery compared with patients without perianal CD (hazard ratio: 1.51, 95% confidence interval [CI]: 1.40 to 1.64, p <0.001) in a multivariate Cox regression analysis. The incidence rate ratios of anal and rectal cancer in perianal CD patients were 11.45 [95% CI: 4.70 to 27.91, p <0.001] and 2.29 [95% CI: 1.25 to 4.20, p = 0.006], respectively, as compared with non-IBD matched controls. Conclusions In this nationwide study, 19% of CD patients developed perianal disease. Patients with perianal CD were at increased risk of undergoing major surgery compared with non-perianal CD patients. The risk of anal and rectal cancer was increased in patients with perianal CD compared with non-IBD matched controls. Podcast This article has an associated podcast which can be accessed at https://academic.oup.com/ecco-jcc/pages/podcast


Author(s):  
Krzysztof Borecki ◽  
Iwona Zawada ◽  
Nermin Nusret Salkić ◽  
Beata Karakiewicz ◽  
Grażyna Adler

It is suggested that IL-23/IL-17 axis and single nucleotide polymorphisms (SNPs) of IL23R may have crucial role in pathogenesis of Crohn’s disease (CD). Thus, we sought to assess the IL23R SNPs contribution to susceptibility and phenotype of CD. We recruited 117 CD subjects and 117 controls from Poland and 30 CD subjects and 30 controls from Bosnia and Herzegovina (B&H). Two common IL23R SNPs: rs1004819, rs7517847 were genotyped using TaqMan SNP assays. In the Polish population it was found that allele rs1004819: A increases the risk of CD, while allele rs7517847: A is protective against disease development. In Poles the co-carriage of two IL23R risk genotypes was associated with increased risk of CD. A significantly increased risk of CD early onset was observed in Poles carrying at least one rs7517847: G allele. It was also found that IL23R SNPs may be associated with structuring/penetrating CD behavior, as alleles rs1004819: A and rs7517847: G were significantly less frequent in patients without complications, from Poland and B&H, respectively. Allele rs1004819: A was also significantly more frequent in Poles with penetrating CD. These results confirm IL23R SNPs contribution to CD susceptibility in the Polish population and suggest their impact on early age of onset and more severe disease course.


2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S51-S52
Author(s):  
William Luo ◽  
Stefan Holubar ◽  
Liliana Bordeianou ◽  
Lynne Crawford ◽  
Bruce Hall ◽  
...  

Abstract Background Ileocolic resection (ICR) is performed for Crohn’s disease (CD) patients with terminal ileitis requiring surgery. Current National Surgical Quality Improvement Program (NSQIP) data is lacking specificity around IBD surgery, including stoma formation and biologic therapies. The NSQIP IBD Collaborative (NSQIP-IBD) is a multicenter working group formed to better collect and analyze perioperative data unique to IBD patients under the auspices of NSQIP. We present retrospective analysis of a multicenter cohort of ICR for CD to describe the current practice of ICR for CD across our collaborative and explore factors associated with rates of postoperative complications on behalf of NSQIP-IBD. Methods Review of NSQIP data from 10 participating sites was performed to select ICR cases for CD from March 2017 to March 2019. In addition to standard data from NSQIP, IBD-specific data regarding stoma formation, immunosuppressant use (biologics, steroids, and immune modulators), and dysplasia is included. Primary outcome was anastomotic leak measured in a 30-day postoperative window in undiverted patients. Secondary outcomes were total non-leak complications and total postoperative infections. Multivariable analysis was performed to adjust for confounding pre- and intraoperative confounders. Backward selection of covariates and factors was performed using a cutoff of p<0.2 for main effects. Results 506 ICR cases for CD were identified. 78 patients had stomas per our unique ileostomy NSQIP-IBD variable, compared to 38 found by querying generally available NSQIP data (48.7% of total stomas). ICR patients receiving stoma were more likely to have more severe ASA class and weight loss and had significantly lower albumin and hematocrit. Age, BMI, and sex were similar in either group. Intraoperatively, stoma patients were more likely have worse wound class, be emergent, and longer operative time. 421 cases had complete baseline and intraoperative data for multivariable analysis of leak rates. 422 were available for secondary outcomes analysis. Multivariable analysis of leak rates showed significant association with infections prior to operation (PATOS; OR=6.6, 95% CI 1.1–40, p=0.041). Significant predictors of total postoperative complication rate and infection rate are shown in Tables 1 and 2, respectively. Conclusions NSQIP-IBD data provides clearer, more detailed data than the NSQIP colectomy module alone in IBD patients. We show that CD ICR patients receiving stomas were more emergent, had intraoperative infection, or had more severe disease. This is consistent with most contemporary surgical practices. Total infections PATOS are associated with increased risk of postoperative anastomotic leak, non-leak complications, and infections. NSQIP-IBD data improves on existing NSQIP data to allow a more robust analysis of factors and outcomes unique to IBD cases. We anticipate with more time and greater numbers we will be able to obtain even more granular data.


2021 ◽  
Vol 14 ◽  
pp. 175628482110048
Author(s):  
Mohamed Attauabi ◽  
Mirabella Zhao ◽  
Flemming Bendtsen ◽  
Johan Burisch

Background: Patients with Crohn’s disease (CD) are at increased risk of co-occurring immune-mediated inflammatory diseases (IMIDs). As discrepancy exists regarding the phenotypic presentation of CD among patients with such co-occurring IMIDs, we aimed to conduct a systematic review with meta-analysis characterizing the phenotype of CD among this subgroup of patients. Methods: PubMed, Embase, and Scopus were searched from their earliest records to October 2019 for studies reporting the behavior and localization of CD according to the Vienna or Montreal Classifications and CD-related surgery in patients with co-occurring IMIDs. These studies were the subject of a random effect meta-analysis. Results: After reviewing 24,413 studies, we identified a total of 23 studies comprising 1572 and 35,043 CD patients with and without co-occurring IMIDs, respectively, that fulfilled our inclusion criteria. Overall, patients with co-occurring IMIDs were more likely to have upper gastrointestinal inflammation than were patients without co-occurring IMIDs [relative risk (RR) = 1.49 (95% confidence interval (CI) 1.09–2.04), p = 0.01, I2 = 7%]. In addition, presence of primary sclerosing cholangitis (PSC) was associated with a lower occurrence of ileal affection [RR = 0.44 (95% CI 0.24–0.81), p < 0.01, I2 = 32%], increased occurrence of colonic affection [RR = 1.78 (95% CI 1.33–2.38), p < 0.01, I2 = 32%] and an increased likelihood of non-stricturing and non-penetrating behavior [RR = 1.43 (95% CI 0.97–2.11), p = 0.07, I2 = 86%]. The latter reached significance when cumulating different IMIDs [RR = 1.30 (95% CI 1.09–1.55), p < 0.01, I2 = 88%]. CD patients with PSC also underwent fewer CD-related surgeries [RR = 0.55 (95% CI 0.34–0.88), p = 0.01, I2 = 0%], irrespective of CD location or behavior. Conclusion: This study emphasizes that CD patients with co-existing PSC are likely to have a unique inflammatory distribution primarily confined to the colon, while patients with IMIDs in general have higher likelihood of affection of upper gastrointestinal tract and a non-stricturing and non-penetrating behavior. As such a phenotype of CD is typically associated with a milder disease course; future studies are needed to confirm these results.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Gao ◽  
Yu Tang ◽  
Na Lei ◽  
Ying Luo ◽  
Pingrun Chen ◽  
...  

AbstractStudies have demonstrated that inflammatory bowel disease (IBD) patients are at an increased risk of developing anxiety and/or depression. IBD patients with depression/anxiety have higher rates of hospitalization and increased disease severity than those without. So far, there is a paucity of data concerning the impact of anxiety/depression on Chinese IBD patients. The aim of this study was to find out the prevalence of symptoms of anxiety/depression in Chinese IBD population and its impact on IBD-related features. This is a cross-sectional study from the southwest China IBD referral center. Eligible participants were divided into those with symptoms of anxiety/depression and those without based on the Hospital Anxiety and Depression Scale (HADS). Demographic data and disease duration, IBD-related surgery, tobacco use, extra-intestinal manifestations, disease activity scores, endoscopic evaluation, laboratory data and current medication use were compared between two groups. A total of 341 IBD patients [221 Crohn’s disease (CD) and 120 ulcerative colitis (UC)] were included. The prevalence of symptoms of anxiety/depression in IBD was 33.1%. CD patients with symptoms of anxiety/depression tended to have higher scores of simple endoscopic scores for Crohn’s disease (SES-CD) (p = 0.0005). UC patients with symptoms of anxiety/depression had a significantly higher Mayo score (p = 0.0017) and ulcerative colitis endoscopic index of severity (UCEIS) (p < 0.0001) than their non-anxiety/depression counterparts. CD-related surgery (p = 0.012) and Crohn's disease activity index (CDAI) (p < 0.0001) were identified as independent risk factors for symptoms of anxiety/depression in CD, while corticosteroid use (p = 0.036) as an independent risk factor for symptoms of anxiety/depression in UC. This study helps our understanding of the prevalence of symptoms of anxiety/depression in IBD patients and its impact on IBD course and reminds us to pay more attention on IBD management with anxiety/depression.


Author(s):  
Gurpreet Malhi ◽  
Parul Tandon ◽  
Jonah Wiseman Perlmutter ◽  
Geoffrey Nguyen ◽  
Vivian Huang

Abstract Background Women with inflammatory bowel disease (IBD) have an increased risk of postpartum disease activity. We aimed to systematically determine the effect of various risk factors on postpartum IBD disease activity. Methods Electronic databases were searched through January 2021 for studies that reported risk of postpartum disease activity in women with IBD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for the impact of IBD phenotype, disease activity, therapy de-escalation, mode of delivery, and breastfeeding on postpartum disease activity. Study bias was determined using the Quality in Prognostic Studies tool. Results Twenty-seven observational studies (3825 patients) were included, 15 of which had a high risk of confounding bias. The pooled incidence of women with postpartum active IBD was 31.9% (95% CI, 25.6–38.1). Similar results were seen with ulcerative colitis and Crohn’s disease (CD; OR, 0.96; 95% CI, 0.58–1.59). Those with stricturing (OR, 3.64; 95% CI, 1.31–10.08) and penetrating (OR, 4.25; 95% CI, 1.11–16.26) CD had higher odds of postpartum active IBD. Active disease at conception (OR, 10.59; 95% CI, 1.48–76.02) and during pregnancy (OR, 4.91; 95% CI, 1.82–13.23) increased the odds of postpartum disease activity. Similarly, biologic discontinuation in the third trimester (OR, 1.77; 95% CI, 1.01–3.10) and therapy de-escalation after delivery (OR, 7.36; 95% CI, 3.38–16.0) was associated with postpartum disease activity. Conclusions Complicated Crohn’s disease, disease activity at conception and during pregnancy, and de-escalation of biologics during pregnancy or after delivery are associated with postpartum disease activity in women with IBD.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S278-S278
Author(s):  
P Lyons ◽  
N Noor ◽  
J C Lee ◽  
E F McKinney ◽  
M Parkes ◽  
...  

Abstract Background Biomarkers predictive of a patient’s future disease course are critical for personalised medicine. There are two Crohn’s disease (CD) assays with validated associations to a clinical outcome; seropositivity for anti-glycan antibodies (AGAs, Glycominds) and a transcriptional signature of T-cell exhaustion (PredictSURE-IBD™, PS-IBD). The optimal time to use these tests would be at diagnosis before bowel damage occurs. As AGAs have primarily been measured in patients after therapy it’s unclear if they provide prognostic information at diagnosis. To address this we performed a head-to-head comparison of both tests in newly diagnosed CD patients. Methods We recruited 74 CD patients with active disease; all patients gave written informed consent and were managed using an accelerated step-up strategy in accordance with international guidelines. Active disease was confirmed by one or more objective marker (raised CRP/calprotectin or endoscopic review) and active symptoms. AGA seropositivity was measured at Addenbrooke’s with the IBDX panel (Glycominds) according to manufacturer’s instructions. Patient stratification was also performed using the PS-IBDtest (PredictImmune Ltd) according to manufacturer’s instructions. Results Most (80%–59/74) patients were newly diagnosed; 58% (43/74) were seropositive for at least 1 AGA, 19% (14/74) were positive for ≥2 AGAs. Newly diagnosed patients had fewer AGAs (51%, 30/59) than previously diagnosed (87%, 13/15) patients (p = 0.018). We stratified patients into two groups based on seropositivity for 2 or more AGAs—associated with an increased risk of more severe disease but found no significant difference in time to, or frequency of, treatment escalation between the groups. Stratification of patients into IBDhi and IBDlo groups with PS-IBDrevealed a significant difference in the subsequent disease course with IBDhi patients experiencing more aggressive disease, characterised by a shorter time to treatment escalation compared with IBDlo patients (p = 0.001). Conclusion AGA seropositivity at diagnosis (as assessed using the IBDX antibody panel) did not predict the need to escalate treatment due to frequently-relapsing or chronically-active disease. Lower AGA seropositivity in newly diagnosed patients compared with those with previous diagnoses suggested that the extent of antibody positivity is a function of disease duration. Previously reported associations between AGA positivity and disease outcome may, therefore, reflect retrospective aggressive disease course and are unlikely to be useful for informing treatment decisions in newly diagnosed patients. The PS-IBD test result correlated with subsequent disease course indicating suitability for early prediction of clinical outcome.


2018 ◽  
Vol 154 (1) ◽  
pp. S56
Author(s):  
Takeo Naito ◽  
Ta-Chiang Liu ◽  
Yoichi Kakuta ◽  
Rintaro Moroi ◽  
Masatake Kuroha ◽  
...  

Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] &lt;150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score &lt;3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.


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