Inflammatory Bowel Diseases最新文献

{"title":"Intestinal Ultrasound Measures are Strongly Correlated With Small Bowel Endoscopic Lewis Score in Active Crohn's Disease.","authors":"Offir Ukashi, Adi Lahat, Bella Ungar, Ido Veisman, Hadar Levy, Kassem Sharif, Pinhas Eidler, Rami Eliakim, Uri Kopylov, Dan Carter, Shomron Ben-Horin, Ahmad Albshesh","doi":"10.1093/ibd/izae296","DOIUrl":"https://doi.org/10.1093/ibd/izae296","url":null,"abstract":"<p><strong>Background: </strong>Small bowel video capsule endoscopy (SB-VCE) assesses mucosal inflammation in Crohn's disease (CD), while intestinal ultrasound (IUS) examines transmural involvement. We aimed to correlate SB-VCE with IUS in evaluating active CD and monitoring treatment response over time.</p><p><strong>Methods: </strong>Patients with active SB-CD who initiated biologics were prospectively followed with fecal calprotectin (FC), SB-VCE, and IUS at baseline and after 14 and 52 weeks. The Lewis score (LS), Limberg index (LI), and terminal ileum bowel wall thickness (TI-BWT) were documented, and the International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) was retrospectively calculated. Biochemical, endoscopic, and ultrasonographic remission were defined as FC < 150 μg/g, LS < 135, and LI < 2 + TI-BWT ≤ 3 mm, respectively. A therapeutic response for each index was defined as a 25% reduction compared to baseline.</p><p><strong>Results: </strong>Seventy-one patients were included (median age: 30 years [23-43], 49.3% male). The median interval between SB-VCE and IUS was 3 days (0-25). Initially, the LS strongly correlated with TI-BWT (r = 0.647, P < .001), LI (r = 0.597, P < .001), and IBUS-SAS (r = 0.647, P < .001), but these correlations weakened over time (TI-BWT: r = 0.344, P = .002; LI: r = 0.471, P = .001; IBUS-SAS: r = 0.236, P = .122). Moderate agreement was found between ultrasonographic and endoscopic treatment responses (LS and TI-BWT: K = 0.51, P = .015; LS and LI: K = 0.44, P = .063), with fair agreement for remission (K = 0.27, P = .006). TI-BWT best cutoffs for mild (LS ≥ 135) and moderate-to-severe (LS ≥ 790) inflammation were 2.25 mm and 3.6 mm, respectively.</p><p><strong>Conclusions: </strong>IUS measures are strongly correlated with VCE-inflammatory LS in active CD and may provide an assessment of endoscopic response and remission over time.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eleven Grand Challenges for Inflammatory Bowel Disease Genetics and Genomics.","authors":"Greg Gibson, John D Rioux, Judy H Cho, Talin Haritunians, Akshaya Thoutam, Maria T Abreu, Steven R Brant, Subra Kugathasan, Jacob L McCauley, Mark Silverberg, Dermot McGovern","doi":"10.1093/ibd/izae269","DOIUrl":"https://doi.org/10.1093/ibd/izae269","url":null,"abstract":"<p><p>The past 2 decades have witnessed extraordinary advances in our understanding of the genetic factors influencing inflammatory bowel disease (IBD), providing a foundation for the approaching era of genomic medicine. On behalf of the NIDDK IBD Genetics Consortium, we herein survey 11 grand challenges for the field as it embarks on the next 2 decades of research utilizing integrative genomic and systems biology approaches. These involve elucidation of the genetic architecture of IBD (how it compares across populations, the role of rare variants, and prospects of polygenic risk scores), in-depth cellular and molecular characterization (fine-mapping causal variants, cellular contributions to pathology, molecular pathways, interactions with environmental exposures, and advanced organoid models), and applications in personalized medicine (unmet medical needs, working toward molecular nosology, and precision therapeutics). We review recent advances in each of the 11 areas and pose challenges for the genetics and genomics communities of IBD researchers.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Surgery Rates in Early Crohn's Disease: Results from a Prospective Population-Based Inception Cohort-The Inflammatory Bowel Disease in South-Eastern Norway III Study.","authors":"Charlotte Lund, Vibeke Strande, Milada Hagen, May-Bente Bengtson, Raziye Boyar, Trond Espen Detlie, Svein Oskar Frigstad, Asle W Medhus, Magne Henriksen, Kristina I Aass Holten, Øistein Hovde, Gert Huppertz-Hauss, Ingunn Johansen, Bjørn Christian Olsen, Randi Opheim, Jens Pallenschat, Gøri Perminow, Petr Ricanek, Roald Torp, Carl Magnus Ystrøm, Ole Høie, Øivind Asak, Simen Vatn, Tone Bergene Aabrekk, Vendel A Kristensen, Marte Lie Høivik","doi":"10.1093/ibd/izae297","DOIUrl":"https://doi.org/10.1093/ibd/izae297","url":null,"abstract":"<p><strong>Background and aims: </strong>The emergence of biologic therapy has coincided with a decline in surgery rates for Crohn's disease (CD). This study aims to describe the disease course, including intra-abdominal surgery rates, biologic therapy use, and variables associated with biologic therapy initiation in a cohort of newly diagnosed CD patients.</p><p><strong>Methods: </strong>The Inflammatory Bowel Disease in South-Eastern Norway (IBSEN) III study is a population-based inception cohort study. From 2017 to 2019, newly diagnosed inflammatory bowel disease patients were included for prospective follow-up. The present study included CD patients ≥ 18 years. Clinical, endoscopic, and demographic data were collected at diagnosis and 1-year follow-up. Data were analyzed by using the Kaplan-Meier method and regression analyses.</p><p><strong>Results: </strong>In total, 424 CD patients (median age 37.0 years (range 18-80), female 55.0%) were included. At diagnosis, 50.5% presented with ileal disease and 80.7% with inflammatory behavior. Within a 1-year follow-up, 39.6% of patients received their first biologic therapy and 5.2% required intra-abdominal surgery. Systemic steroid treatment, CRP ≥ 5.0 mg dL-1, Harvey-Bradshaw Index score > 4, ileocolonic disease and penetrating disease behavior at diagnosis were independently associated with increased risk of initiation of biologic therapy, while age > 40 years was associated with decreased risk.</p><p><strong>Conclusion: </strong>A high proportion of patients had ileal disease and inflammatory behavior at diagnosis. Still, nearly 40% started biologic therapy within the 1-year follow-up, while only 5% required intra-abdominal surgery.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Toward Transmural Healing in Pediatric Crohn's Disease.","authors":"Sara Lega, Matteo Bramuzzo","doi":"10.1093/ibd/izae224","DOIUrl":"https://doi.org/10.1093/ibd/izae224","url":null,"abstract":"","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improvement of Transmural Inflammation With Adalimumab Versus Immunomodulator Maintenance Therapy in Pediatric Crohn's Disease: Single-Center Prospective Evaluation Using the Pediatric Inflammatory Crohn's Magnetic Resonance Enterography Index.","authors":"Luca Scarallo, Hayley E McKay, Rilla Schneider, Amanda Ricciuto, Thomas D Walters, Mary-Louise C Greer, Anne M Griffiths, Peter C Church","doi":"10.1093/ibd/izae227","DOIUrl":"https://doi.org/10.1093/ibd/izae227","url":null,"abstract":"<p><strong>Background and aims: </strong>Transmural healing, including as assessed by magnetic resonance enterography (MRE) has been associated with long-term favorable outcomes in Crohn's Disease (CD), but data concerning MRE improvement and normalization with therapy are sparse. We performed a prospective longitudinal study utilizing the recently developed pediatric MRE-based multi-item measure of inflammation (PICMI) to examine the efficacy of adalimumab (ADA) and immunomodulator (IM) in attaining improvement of transmural inflammation of the small intestine.</p><p><strong>Methods: </strong>Pediatric patients with CD involving small bowel and initiating ADA or IM were prospectively enrolled and followed with repeat MRE at 1 year. A single radiologist provided global assessment (RGA) and scored PICMI items (wall thickness, wall diffusion restriction, mural ulcers, comb sign, mesenteric edema) blinded to clinical information and to the timing of MRE. The primary outcome was mild improvement in PICMI at one year without a change in therapy.</p><p><strong>Results: </strong>Sixty-two eligible patients were enrolled, 26 receiving ADA and 36 IM. On intent to treat basis, a decline in PICMI score of >20 points without change of therapy was observed more frequently in ADA versus IM-treated patients (54% vs 31%, P = .01). By RGA, 71% improved with ADA vs 42% with IM (P = .03). MRE normalization was rare with both treatments (9% vs 6%, P = .62). A change in PICMI of >20 points was confirmed as the best cut off for MRE improvement as assessed by RGA also for the small bowel.</p><p><strong>Conclusions: </strong>ADA therapy was associated with objective improvement in MRE findings of inflammation more frequently than IM. The low rate of MRE normalization suggests that this is not yet a realistic target with existing therapies.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights into the Pathogenesis of Intestinal Fibrosis in Inflammatory Bowel Diseases: Focusing on Intestinal Smooth Muscle Cells.","authors":"Maria Kalafateli, Evanthia Tourkochristou, Efthymios P Tsounis, Ioanna Aggeletopoulou, Christos Triantos","doi":"10.1093/ibd/izae292","DOIUrl":"https://doi.org/10.1093/ibd/izae292","url":null,"abstract":"<p><p>Strictures in inflammatory bowel disease, especially Crohn's disease (CD), are characterized by increased intestinal wall thickness, which, according to recent accumulating data, is mainly attributed to the expansion of the intestinal smooth muscle layers and to a lesser extent to collagen deposition. In this review, we will discuss the role of intestinal smooth muscle cells (SMCs) as crucial orchestrators of stricture formation. Activated SMCs can synthesize extracellular matrix (ECM), thus contributing to intestinal fibrosis, as well as growth factors and cytokines that can further enhance ECM production, stimulate other surrounding mesenchymal and immune cells, and increase SMC proliferation via paracrine or autocrine signaling. There is also evidence that, in stricturing CD, a phenotypic modulation of SMC toward a myofibroblast-like synthetic phenotype takes place. Moreover, the molecular mechanisms and signaling pathways that regulate SMC hyperplasia/hypertrophy will be extensively reviewed. The understanding of the cellular network and the molecular background behind stricture formation is essential for the design of effective anti-fibrotic strategies, and SMCs might be a promising therapeutic target in the future.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gender and Sex Differences in Abdominal Pain, Fatigue, And Psychological Symptoms Among Adults with Inflammatory Bowel Disease: A Network Analysis.","authors":"Kendra Kamp, Pei-Lin Yang, Chi-Shan Tsai, Xiaoyu Zhang, Linda Yoo, Molly R Altman, Margaret Heitkemper, Samantha Conley, Sunanda Kane, Samantha Winders","doi":"10.1093/ibd/izae279","DOIUrl":"https://doi.org/10.1093/ibd/izae279","url":null,"abstract":"<p><strong>Background and aims: </strong>Individuals with inflammatory bowel disease (IBD) experience a high symptom burden, including abdominal pain, fatigue, anxiety, depression, and sleep disturbances; yet, little is known regarding the relationship between sex and gender on symptoms. We sought to report symptom severity for cisgender men, cisgender women, and transgender and gender-diverse (TGD) individuals. In addition, we used network analysis to identify core symptoms and explore if symptoms and their relationships differ between cisgender men and cisgender women.</p><p><strong>Methods: </strong>This was a cross-sectional study. We recruited adults with IBD online through ResearchMatch. Individuals responded to Patient-Reported Outcomes Measurement Information symptom questionnaires, as well as demographic and clinical questionnaires. Network analysis was used to identify the core symptoms driving the symptom structure.</p><p><strong>Results: </strong>One-hundred and fifty-seven (63.3%) participants identified as cisgender women, 84 (33.9%) as cisgender men, and 7 (2.8%) as TGD. Cisgender men (M = 61.8) and TGD (M = 61.3) groups reported higher abdominal pain levels compared with cisgender women (M = 57.8; P = .02). Transgender and gender-diverse individuals reported higher depression levels (M = 64.8) compared with cisgender men (M = 56.7) and cisgender women (M = 54.4; P = .01). Using a network analysis approach, anxiety and fatigue emerged as core symptoms for the entire sample (clinically active and inactive disease), and among only those with active clinical disease. Fatigue was a top core symptom for cisgender women; anxiety emerged as a top core symptom for cisgender men.</p><p><strong>Conclusions: </strong>This study highlights that fatigue and anxiety are core symptoms among individuals with IBD and demonstrates a potential sex and/or gender difference in core symptoms. Replication of this study is needed with further consideration of inclusion of TGD patients.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Etrasimod as a Monotherapy or With Concomitant Use of Corticosteroids and/or Aminosalicylates: Results From the ELEVATE UC Clinical Program.","authors":"Andres J Yarur, Michael V Chiorean, Jessica R Allegretti, Raymond K Cross, Christina Ha, Martina Goetsch, Aoibhinn McDonnell, Alexis B Dalam, Joseph Wu, David A Blanco, Arcangelo M Abbatemarco, Julian Panés","doi":"10.1093/ibd/izae288","DOIUrl":"https://doi.org/10.1093/ibd/izae288","url":null,"abstract":"<p><strong>Background: </strong>Etrasimod is an oral, once daily (QD), selective sphingosine 1-phosphate1,4,5 receptor modulator for the treatment of moderately to severely active ulcerative colitis (UC). We assessed the benefit of etrasimod monotherapy and the impact of concomitant corticosteroids (CS) and/or 5-aminosalicylates (5-ASA) therapy.</p><p><strong>Methods: </strong>In ELEVATE UC 52 and ELEVATE UC 12, patients with moderately to severely active UC were randomized 2:1 to etrasimod 2 mg QD or placebo for 52 and 12 weeks, respectively. Oral CS or 5-ASA were allowed at baseline. Patients in the monotherapy subgroup received etrasimod or placebo without concomitant CS and/or 5-ASA at baseline. Predefined primary (clinical remission) and key secondary efficacy endpoints aligned with those from both trials and were assessed at Week 12 and Week 52. Safety was assessed up to Week 52.</p><p><strong>Results: </strong>Clinical remission rates at Weeks 12 and 52 were significantly higher for etrasimod compared with placebo in patients receiving monotherapy (Week 12: 26.2% vs 4.8%; Week 52: 35.7% vs 4.0%). Differences vs placebo were statistically significant for all predefined endpoints at both time points in patients receiving monotherapy or etrasimod with concomitant 5-ASA only (all P < .05); numerical differences, due to small sample sizes, vs placebo were observed for all endpoints in the CS only and CS + 5-ASA subgroups. Safety was consistent with the overall population.</p><p><strong>Conclusions: </strong>Etrasimod monotherapy showed consistent efficacy and safety vs placebo; no apparent benefit was observed with concomitant CS and/or 5-ASA in patients receiving etrasimod.</p><p><strong>Clinical trial registration: </strong>NCT03945188; NCT03996369.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selecting High-Risk Patients With Pediatric Crohn's Disease for Top-Down Anti-TNF as per the 2021 ECCO-ESPGHAN Guidelines: A 5-Year Nationwide Retrospective Analysis From Scotland (2016-2020).","authors":"Gregor Scott, David I F Wands, David C Wilson, Richard Hansen, Iain Chalmers","doi":"10.1093/ibd/izae298","DOIUrl":"https://doi.org/10.1093/ibd/izae298","url":null,"abstract":"<p><strong>Background: </strong>The 2021 ECCO-ESPGHAN guideline on the medical management of pediatric Crohn's disease promotes early risk stratification and top-down anti-TNF for patients deemed high risk of severe disease course.</p><p><strong>Aims: </strong>We aimed to objectively assess the risk-benefit profile of the guideline's risk stratification policy and guidance on top-down anti-TNF in a nationwide population-based cohort study.</p><p><strong>Methods: </strong>Using a prospectively identified nationwide cohort of all new pediatric patients (<17 years) diagnosed with Crohn's disease in Scotland between January 1, 2016 and December 31, 2020 and retrospectively applying the current management algorithm, we explored the guideline's ability to accurately risk stratify patients. Phenotypic and treatment data were retrospectively collected from electronic medical records with a maximum follow-up of 18 months post-diagnosis.</p><p><strong>Results: </strong>Four hundred and eighteen children (258/418 [62%] male; median [interquartile range {IQR}] age at diagnosis: 13.2 [11.2-14.8] years) were included. High-risk phenotype was present in 224/418 (54%) with 53/224 (24%) of high-risk patients not requiring anti-TNF therapy within 18 months of diagnosis. Conversely, 78/194 (40%) of the low-risk group received anti-TNF within 18 months. High-risk patients were more likely to require anti-TNF (171/224 [76%] vs 78/194 [40%], P < .001) and had shorter median (IQR) time to anti-TNF start (5.0 [1.0-8.0] months vs 6.5 [3.3-13.0] months, P = .01).</p><p><strong>Conclusions: </strong>Our data support the guideline's ability to identify patients more likely to require early treatment escalation. However, this approach would have led to potential over- and under-treatment in a substantial proportion of patients. This underscores the importance of frequent and comprehensive monitoring, along with flexible treatment strategies that adapt to changes in disease status.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MIP4IBD: An Easy and Rapid Genotyping-by-Sequencing Assay for the Inflammatory Bowel Diseases Risk Loci.","authors":"Sare Verstockt, Laurens Hannes, Deborah Sarah Jans, Stephanie Deman, Erika Souche, Ilse van der Werf, Liv Vandermeulen, Triana Lobaton, Debby Laukens, Bram Verstockt, Jeroen Van Houdt, Alexander Hoischen, Séverine Vermeire, Isabelle Cleynen","doi":"10.1093/ibd/izae289","DOIUrl":"https://doi.org/10.1093/ibd/izae289","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel diseases (IBD) are polygenic, with many genetic variants contributing to disease risk. Knowing the genotype of specific variants or calculating a combined genetic risk score benefits translational and functional research. To address this, we developed MIP4IBD, a flexible and cost-effective genotyping-by-sequencing assay using molecular inversion probes (MIPs).</p><p><strong>Methods: </strong>The assay targets 463 IBD risk variants, and 77 additional relevant variants. Molecular inversion probes capture and library preparation were optimized using 15 IBD DNA samples, comparing genotypes with immunochip. A custom GitHub pipeline was created for data processing, performance testing, and genotype calling. The final design was validated on a larger scale (149 IBD patients, 104 non-IBD controls, and 3 external cell lines), incorporating post hoc quality control criteria.</p><p><strong>Results: </strong>The assay achieved a 3.5-day turnaround time at €15 per sample with optimal sample throughput, demonstrating a 92.6% success rate in variant capture and genotype concordance rates of 99.3% and 99.6% with Infinium Global Screening Array24 BeadChip and WGS, respectively. A downstream application involved the calculation of a weighted IBD polygenic risk score (PRS), which was significantly higher in IBD patients than controls (mean 0.42 vs -0.49, P = 1.95E-11). Individuals in the highest PRS quartile had a 15.7-fold (95% CI: 6.5-38.3) risk of developing IBD and an earlier age of onset (26 vs 37 years, P = 0.02), compared to the lowest quartile.</p><p><strong>Conclusions: </strong>MIP4IBD is a validated, scalable genotyping assay targeting IBD risk loci, with an integrated bioinformatics pipeline from sequencing data to genotypes and PRS calculation. Its cost-effectiveness and flexibility for additional variants make it particularly appealing for translational and clinical applications.</p>","PeriodicalId":13623,"journal":{"name":"Inflammatory Bowel Diseases","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}