Journal of Crohn's & colitis最新文献

{"title":"Gene-Environment Interactions in Inflammatory Bowel Disease: A Systematic Review of Human Epidemiologic Studies.","authors":"Jingjing Bai, Dianne Gelien Bouwknegt, Rinse Karel Weersma, Gerard Dijkstra, Kimberley Wilhelmina Johanna van der Sloot, Eleonora Anna Margaretha Festen","doi":"10.1093/ecco-jcc/jjaf061","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf061","url":null,"abstract":"<p><strong>Background and aims: </strong>Complex gene-environment interaction (GXE) for inflammatory bowel disease (IBD) remains elusive. This systematic review aims to summarize the current evidence of GXE in IBD.</p><p><strong>Methods: </strong>PubMed, EMBASE, Web of Science, and Scopus were systematically searched from inception through April 30, 2024, to identify publications examining the interaction effect of genetic variants and environmental factors in IBD. All eligible studies were graded using STREGA guideline.</p><p><strong>Results: </strong>Four thousand eight hundred thirty-three publications were identified and screened, resulting in 39 eligible studies, and 17 studies reported statistically significant interactions. NOD2-smoking interaction was most frequently investigated and showed variant-specific effect at rs2066847 regarding the risk of Crohn's disease. Gene-smoking interactions were further identified in other IBD risk genes (ATG16L1, IL23R, and CALM3), detoxification genes (GSTP1 and HMOX1), smoking-associated genes (CHRNA3, CHRNA5, PPP1R3C, and BDNF), and the inflammatory cytokine (IL1B) through a candidate gene approach. Immunochip-wide interaction analyses yielded 64 smoking interacting variants. Gene-diet interactions were observed across multiple nutritional measures, including fatty acid intake with CYP4F3 and FADS2, serum selenium with SEPHS1 and SEPSECS, potassium intake with IL21, alcohol consumption with IL12B, heme iron intake with FCGR2A, and serum vitamin D with VDR.</p><p><strong>Conclusions: </strong>Current evidence indicated that the IBD risk conferred by environmental factors can vary among the individuals carrying certain genetic variants. Further efforts, including genome wide environment interaction studies and genotype-based nutrition/lifestyle clinical trials, are needed to unravel the missing heritability influenced by environmental exposures and to construct personalized recommendations of lifestyle/dietary modification based on an individual genetic background.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":"19 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcutaneous infliximab (CT-P13 SC) as maintenance therapy for Crohn's disease and ulcerative colitis: 2-year results from open-label extensions of two randomized controlled trials (LIBERTY).","authors":"Jean-Frederic Colombel, William J Sandborn, Stefan Schreiber, Silvio Danese, Maria Kłopocka, Jarosław Kierkuś, Roman Kulynych, Maciej Gonciarz, Artur Sołtysiak, Patryk Smoliński, Slobodan Srećković, Ekaterina Valuyskikh, Adi Lahat, Marek Horyński, Antonio Gasbarrini, Marina Osipenko, Vladimir Borzan, Maciej Kowalski, Daria Saenko, Ruslan Sardinov, Sang Joon Lee, Sunghyun Kim, Yunju Bae, Sunhee Lee, Seulgi Lee, Joon Ho Lee, Jong Min Kim, Gahee Park, Jimin Lee, Juhyun Lee, Jae Yeoul Ryu, Bruce E Sands, Stephen B Hanauer","doi":"10.1093/ecco-jcc/jjaf060","DOIUrl":"10.1093/ecco-jcc/jjaf060","url":null,"abstract":"<p><strong>Background and aims: </strong>In the LIBERTY phase 3 studies in Crohn's disease (CD) or ulcerative colitis (UC), maintenance CT-P13 subcutaneous (SC) 120 mg was more effective than placebo after 1 year. Here we report 2-year data from the LIBERTY open-label extensions.</p><p><strong>Methods: </strong>Two randomized, placebo-controlled, double-blind studies evaluated the efficacy and safety of CT-P13 SC maintenance in moderate-to-severe CD or UC. Responders to CT-P13 intravenous induction were randomized at week (W) 10 to CT-P13 SC 120 mg or placebo biweekly, until W54. From W22, dose adjustment to CT-P13 SC 240 mg was permitted for loss of response. At W56, patients could enter an open-label extension, receiving CT-P13 SC 120 mg (or 240 mg if dose-adjusted), biweekly, until W102.</p><p><strong>Results: </strong>The extension comprised 278/343 (81.0%) and 348/438 (79.5%) patients in the CD and UC studies, respectively. In those continuing on-study, efficacy (non-responder imputation) was well maintained in the CT-P13 SC group at W102: 63.5% (as-observed: 70.5%) and 49.0% (as-observed: 58.8%) of CD patients (N = 192) achieved clinical remission and endoscopic response, respectively; 45.1% (as-observed: 60.1%) and 41.4% (as-observed: 52.4%) of UC patients (N = 237) achieved clinical remission and endoscopic-histologic mucosal improvement, respectively. No new safety signals were identified from longer-term CT-P13 SC treatment or starting CT-P13 SC 120 mg after placebo, with similar adverse event rates for patients undergoing dose adjustment to CT-P13 SC 240 mg from CT-P13 SC 120 mg or placebo.</p><p><strong>Conclusion: </strong>CT-P13 SC is an effective and well-tolerated long-term maintenance treatment in moderate-to-severe CD and UC.</p><p><strong>Clinicaltrials.gov identifiers: </strong>NCT03945019 (CD) and NCT04205643 (UC).</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term disease course of ulcerative colitis in a prospective European population-based inception cohort - an Epi-IBD cohort study.","authors":"Mads Damsgaard Wewer, Søren Lophaven, Peter L Lakatos, Lorant Gonczi, Riina Salupere, Hendrika Adriana Linda Kievit, Kári Rubek Nielsen, Jóngerð Midjord, Viktor Domislovic, Željko Krznarić, Natalia Pedersen, Jens Kjeldsen, Jonas Halfvarson, Shaji Sebastian, Adrian Goldis, Naila Arebi, Pia Oksanen, Anders Neumann, Vibeke Andersen, Konstantinos H Katsanos, Anastasios Koukoudis, Svetlana Turcan, Pierre Ellul, Juozas Kupcinskas, Gediminas Kiudelis, Mathurin Fumery, Ioannis P Kaimakliotis, Renata D'Inca, Silvia Lombardini, Vicent Hernandez, Alberto Fernandez, Ebbe Langholz, Pia Munkholm, Johan Burisch","doi":"10.1093/ecco-jcc/jjaf089","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf089","url":null,"abstract":"<p><strong>Background and aims: </strong>The Epi-IBD cohort is a population-based inception cohort of patients with inflammatory bowel disease from 22 European centres. The aim was to assess the 10-year disease course of patients with ulcerative colitis (UC) across Europe.</p><p><strong>Methods: </strong>Patients were followed prospectively from the time of diagnosis in 2010 and 2011, with uniform collection of data to end of 2020. Associations between covariates and colectomy, progression to extensive disease and hospitalisation were analysed separately by multivariable Cox regression analyses in a propensity score-matched sub-population to address regional differences.</p><p><strong>Results: </strong>A total of 873 UC patients were recruited (Eastern Europe: 196 (22.4%), Western Europe: 677 (77.5%)). The 10-year crude rate for the use of advanced therapy was comparable in Eastern (13%) and in Western Europe (16%) (p>0.9), and the median time from diagnosis until initiation of advanced treatment was similar, at three years. The need for colectomy remained comparable in Eastern and Western Europe, with a 10-year crude rate of 4% and 6% (Cox:p=0.6), respectively. Likewise, disease progression to extensive disease (10-year rate: 17%, Cox:p=0.06) and hospitalisation (10-year rate: 23%, Cox:p=0.2) were comparable across Europe. The use of advanced therapy, and the early use of corticosteroids, were both associated with an increased risk of colectomy (Cox:both p<0.05).</p><p><strong>Conclusions: </strong>While the introduction of advanced therapies for UC has transformed the therapeutic landscape, their impact on colectomy rates, disease progression, and hospitalisations remains modest. Our findings highlight the need for continued innovation in UC treatment and the importance of individualised and targeted care to achieve optimal long-term outcomes.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer Incidence in Patients with Ulcerative Colitis Naïve to or Treated with Thiopurine and Targeted Therapies- a cohort study 2007 to 2022 with comparison to the general population.","authors":"Åsa H Everhov, Johan Askling, Jonas Söderling, Jonas Halfvarson, Julia Eriksson, Karin E Smedby, Jonas F Ludvigsson, Henrik Toft Sørensen, Ola Olén","doi":"10.1093/ecco-jcc/jjaf091","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf091","url":null,"abstract":"<p><strong>Background: </strong>Cancer incidence data including absolute risk differences are needed for clinical risk communication to patients receiving modern-day treatments for ulcerative colitis (UC).</p><p><strong>Methods: </strong>We linked nationwide Swedish health registers and assessed incident cancers in patients with UC in 2007-2022. We computed age-stratified incidence rates (IRs), IR differences and hazard ratios (HRs) in a naïve cohort with no immunomodulatory treatment, and in cohorts treated with thiopurine or targeted therapies. General population comparator subjects were matched (by age, sex, calendar year, and area of residence) to each treatment cohort. We used a once-exposed - always exposed design.</p><p><strong>Results: </strong>We identified 63,925 patients with UC in partly overlapping cohorts and 593,072 comparators with a total follow-up time of 5,800,089 years (median 8.1 years).The IRs were elevated compared to the general population in naïve patients: 2.7 extra cancer cases per 1000 person years (HR:1.12, 95%CI:1.09-1.16), in thiopurine-treated patients: 3.4 extra cases (HR:1.48;1.37-1.61), TNFi-treated: 2.7 extra cases (HR:1.41;1.24-1.62), Thiopurine+TNFi-treated: 2.42 extra cases (HR:1.44;1.19-1.75), vedolizumab-treated: 2.88 extra cases (HR:1.27;0.90-1.79). The IR differences were not significantly increased in patients treated with ustekinumab 0.57 (HR:0.87;0,39-1.93) and tofacitinib -0.69 (HR:0.84;0.25-2.77). Across all treatment groups, the IR differences compared to the general population were highest in patients ≥60 years. The differences were driven by colorectal cancer, hepatobiliary cancer, lymphoma, and basal cell skin carcinoma.</p><p><strong>Conclusion: </strong>Elevated cancer incidence was observed in patients with UC amounting to around 3 extra cases of cancer per 1000 years. Cancer risks varied more among groups defined by age than by treatment.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact Of Immunomodulating Medication On Maternal Tdap Vaccination Induced Antibodies In Infants.","authors":"Jantien W Wieringa, Mirjam J Esser, Gerco den Hartog, M Alina Nicolaie, Lyanne W Rövekamp, Esther G J Rijntjes-Jacobs, Ron H T van Beek, Gerdien A Tramper-Stranders, Marjan Kuijer, Maarten M Immink, Nicoline A T van der Maas, Nynke Y Rots, Gertjan J A Driessen","doi":"10.1093/ecco-jcc/jjaf090","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf090","url":null,"abstract":"<p><strong>Background and aims: </strong>Current international guidelines on inflammatory bowel disease (IBD) advise to continue immunomodulating medication during pregnancy. Data on the effect of this medication on maternal Tdap (Tetanus-Diphtheria-acellular pertussis) vaccination and transfer of antibodies to the infant are scarce.</p><p><strong>Methods: </strong>Pregnant women with IBD receiving various immunomodulating medications and their infants were prospectively recruited in the PETIT study cohort from 16 hospitals in the Netherlands between December 2018 and March 2023. All women were offered maternal Tdap vaccination according to the Dutch National Immunization Program. IgG concentrations against all Tdap components were measured at birth (maternal- and cord-blood) and at 2 months of age in the infant, preceding active immunization. We compared Geometrical Mean Concentrations (GMCs) in IBD-mother-infant-pairs with healthy control mother-infant-pairs.</p><p><strong>Results: </strong>GMCs of antibodies against all Tdap components were significantly higher in 135 maternally vaccinated mothers and their infants compared with 25 unvaccinated IBD-women-infant pairs treated with immunomodulating medication during pregnancy, at all timepoints. However, GMC against PRN was significantly lower in vaccinated IBD-mother-infant pairs compared to healthy vaccinated control mother-infant-pairs, particularly in mothers treated with anti-Tumor Necrosis Factor alpha (anti-TNFα) and their infants.</p><p><strong>Conclusions: </strong>Maternal Tdap vaccination in women with IBD receiving immunomodulating medication during pregnancy results in significantly higher Tdap-antibody concentrations in their infants compared to infants of unvaccinated IBD mothers, although GMC was lower for PRN compared to healthy controls. These results support current recommendations to advise maternal Tdap vaccination in pregnant women receiving immunomodulating medication.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Immune Profiling of Crohn's Disease Fistula Carcinomas - Defining a Distinct Cancer Subtype.","authors":"Malte Lehmann, Daniela Paclik, Adrian Huck, Alexander Arnold, Clemens Kurth-Stavenhagen, Michael Vieth, Christoph Treese, Anja A Kühl, Britta Siegmund","doi":"10.1093/ecco-jcc/jjaf086","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf086","url":null,"abstract":"<p><strong>Background & aims: </strong>Fistula formation is a common and debilitating complication in Crohn's disease (CD). CD-associated fistula carcinomas, though rare, pose diagnostic and prognostic challenges. This study aims to identify disease-defining immune cell subsets in CD-associated fistula carcinomas.</p><p><strong>Methods: </strong>The study included tissue samples from 10 CD patients with fistula carcinomas, 7 with CD-associated fistulas, and 6 with sporadic colorectal cancer (CRC). The main tumor, infiltration front, and non-involved areas were analyzed in tumor samples. A 36-marker panel was employed to define the immune landscape using imaging mass cytometry. Samples were processed, stained, and analyzed for immune cell compositions, cell-cell interactions, and spatial microenvironments.</p><p><strong>Results: </strong>The immune infiltrate in fistula carcinomas shared similarities with both CD fistulas and CRC. Fistula-carcinoma samples exhibited high levels of neutrophils, B cells, and CD163high macrophages. CRC main tumor samples showed an increased presence of intraepithelial CD8+ lymphocytes and CD163low macrophages. Cleaved Caspase-3 levels were highest in CRC main tumor samples, correlating positively with CD163low macrophages and cytotoxic T cells. In contrast, fistula-carcinoma main tumor samples showed a negative correlation between cleaved Caspase-3 and cytotoxic T cells. Analysis of cellular microenvironments and dimensionality reduction clustering based on immune cell frequencies indicated fistula-carcinomas to exhibit a mixture of immune cell characteristics from both CD fistulas and CRC.</p><p><strong>Conclusions: </strong>The immune landscape of CD-associated fistula carcinomas exhibits features of both CD fistulas and CRC, suggesting a complex pathogenesis influenced by chronic inflammation. Our data suggest that fistula carcinomas represent a unique cancer subtype, that requires further analysis to develop targeted therapeutic strategies.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of Janus kinase inhibitors for the management of fibrosis in inflammatory bowel disease.","authors":"J Su, D A Lartey, G Zanella, L J A C Hawinkels, G Matteoli, M Löwenberg, M C Barnhoorn","doi":"10.1093/ecco-jcc/jjaf087","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf087","url":null,"abstract":"<p><p>Intestinal fibrosis in inflammatory bowel disease (IBD) is caused by uncontrolled accumulation of extracellular matrix deposited by fibroblasts. This may result in stricture formation, especially in Crohn's disease. Since there are no anti-fibrotic drugs available, endoscopic or surgical interventions are the only options to treat intestinal strictures. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway plays a crucial role in intestinal homeostasis and inflammation. JAK inhibition represents a relative novel therapeutic strategy in IBD by simultaneously blocking multiple cytokines across various inflammatory pathways. Interestingly, JAK inhibitors extend their benefits beyond anti-inflammatory effects, as they have been shown to interfere with fibrotic processes in various diseases, including IBD. We here summarize the current understanding of the role of the JAK-STAT pathway in the pathogenesis of intestinal fibrosis and the application of JAK inhibitors for IBD. In addition, we discuss the use of JAK inhibitors in other fibrotic-related diseases to postulate how these agents might be applied for future treatment of intestinal fibrosis.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Restoring Prostacyclin/PGI2-PTGIR Signaling Alleviates Intestinal Fibrosis in Crohn's Disease via Fibroblast-specific YAP/TAZ Inhibition.","authors":"Weijun Ou, Yaosheng Wang, Weimin Xu, Zhebin Hua, Xiaolei Wang, Wensong Ge, Wenjun Ding, Yingwei Chen, Chen-Ying Liu, Peng Du","doi":"10.1093/ecco-jcc/jjaf084","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf084","url":null,"abstract":"<p><strong>Background and aims: </strong>Intestinal obstruction caused by fibrosis is a common and serious complication of Crohn's disease (CD). Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motifs (TAZ), the transcriptional effectors of the Hippo signaling pathway, have emerged as key drivers of intestinal fibrosis. Systematic inhibition of YAP/TAZ failed to combat fibrotic progression, probably due to the vital of epithelial YAP/TAZ in intestinal homeostasis.</p><p><strong>Methods: </strong>ELISA and immunohistochemical staining were used to detect serum Prostaglandin I2 (PGI2) levels and PGI2 Receptor (PTGIR) in clinical samples derived from CD patients. Dual luciferase reporter and Cut & Run assays were performed to explore the transcriptional regulatory mechanisms of PTGIR and PGI2 synthase (PTGIS) by TNF-α and TGF-β, respectively. Primary intestinal fibroblasts and a chronic colitis model were used for assessing the efficacy of a PTGIR agonist in combating fibrosis.</p><p><strong>Results: </strong>The Gαs-coupled PTGIR is expressed in intestinal fibroblasts but is barely expressed in intestinal epithelial cells (IECs). PTGIR transcription is directly activated by p65 in fibroblasts upon TNF-α stimulation. Importantly, PTGIS is transcriptionally suppressed by TGF-β, leading to the loss of endogenous antifibrotic PGI2-PTGIR signaling. Serum PGI2 levels are decreased in CD patients with stenosis and are negatively correlated with disease duration. The PTGIR agonist inhibited the profibrotic function of YAP/TAZ in intestinal fibroblasts in vitro and reversed intestinal fibrosis in vivo.</p><p><strong>Conclusions: </strong>The antifibrotic effects of PGI2-PTGIR signaling are impaired in CD. Restoring PGI2-PTGIR signaling is a pharmacologically tractable and cell-selective approach to targeting YAP/TAZ via PTGIR, which reverses intestinal fibrosis.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum Biomarkers of Collagen Remodeling are Associated with Intestinal Fibrosis and Differentiates Stenotic from Luminal Crohn's Disease Patients: A Pre- and Post-Resection Longitudinal Study.","authors":"Anja Poulsen, Marta Sorokina Alexdóttir, Lene Buhl Riis, Pernille Dige Ovesen, Julie Rasmussen, Mads Damsgaard Wewer, Viviane Lin, Ronja M B Lagström, Marwah Al-Sheikh, Emilie Dahl, Annedorte Ries, Martin Pehrsson, Thomai Tsapanou-Katranara, Peter-Martin Krarup, Ismail Gögenur, Florian Rieder, Johan Burisch, Joachim Høg Mortensen, Jakob Benedict Seidelin","doi":"10.1093/ecco-jcc/jjaf085","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf085","url":null,"abstract":"<p><strong>Background and aims: </strong>Crohn's disease (CD) is characterized by progressive intestinal transmural damage, including fibrosis and strictures, which impair quality of life and require surgical intervention. No anti-stricture therapies are available, and no accurate biomarkers have been validated allowing prediction of strictures. Collagen fragments synthesis and remodeling show potential as markers of transmural disease activity. This study aimed to evaluate serum collagen markers for their accuracy in differentiating between stenosing and luminal CD and assessing their correlation with histopathology.</p><p><strong>Methods: </strong>Sixty-two patients undergoing resection for stricturing CD and 49 with luminal CD were prospectively included. ECM markers were quantified using ELISA, and histological assessments of fibrosis and inflammation were performed on full-thickness tissue samples. Clinical outcomes, biomarkers, and histology were analyzed over a 12-month follow-up.</p><p><strong>Results: </strong>ECM markers, including PRO-C6, PRO-C3, PRO-C5, C4M, and PRO-C4, distinguished stenosing from luminal CD with and the combination of PRO-C6, PRO-C3, and PRO-C5 achieved the highest discriminative power of (AUC 0.91). Significant changes in levels of the collagen biomarker were observed post-resection. Histological analysis revealed extensive intestinal fibrosis in the submucosa of the stenotic segments, which correlated with PRO-C6 levels. C4M and PRO-C4 positively correlated with neutrophils in lamina propria. CTX-III correlated negatively to the D'Haens score and neutrophils -and mononuclear cells in lamina propria and in epithelium.</p><p><strong>Conclusion: </strong>Collagen markers distinguished stenosing from luminal CD, and they correlated to histological fibrosis and chronic inflammation promising for understanding ECM remodeling. This study highlights the need for extended follow-up to assess long-term stenosis-related outcomes.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The angiotensin receptor blocker, losartan, reduces inflammation and fibrosis, and prevents relapse of fibrosis after steroid-induced remission, in mice prone to Crohn's disease-like ileitis.","authors":"Serena Artone, Shuvra Ray, Joseph J Williams, Kenan Akbulut, Paul Cordero, Ana M Gómez-Úriz, Hannah R Friedman, Anna V Saline, Isabel M Hart, Elakia Vadivelan, Tommaso L Parigi, Davide Pietropaoli, Giovanni Latella, Jeremy D Sanderson, Carlo De Salvo, Jude A Oben, Theresa T Pizarro, Stefania De Santis","doi":"10.1093/ecco-jcc/jjaf083","DOIUrl":"https://doi.org/10.1093/ecco-jcc/jjaf083","url":null,"abstract":"<p><strong>Background and aims: </strong>The renin-angiotensin system is known to modulate fibrosis, which is a common complication of ileal Crohn's disease. We tested the efficacy of losartan, an angiotensin receptor blocker, to treat intestinal fibrosis in relevant pre-clinical models of Crohn's-like disease.</p><p><strong>Methods: </strong>Effector molecules of the renin-angiotensin system were mined in a large publicly-available RNA-Seq dataset of intestinal biopsies from Crohn's patients and healthy individuals, and presence of associated proteins confirmed by immunohistochemistry in full-thickness intestinal tissues. Losartan's efficacy in altering mediators of the renin-angiotensin system and of fibrosis was tested in vitro using activated CCD-18Co fibroblasts, while its in vivo effects were investigated by administering losartan to SAMP1/YitFc mice, a well-described model of Crohn's-like disease that progressively develops both ileal-specific inflammation and fibrosis, using either therapeutic or maintenance of remission (treatment after dexamethasone) approaches.</p><p><strong>Results: </strong>Angiotensinogen, an upstream regulator of the renin-angiotensin system, and the downstream effector, angiotensin II receptor type 1, expressed on target cells, are both increased in involved vs. non-involved gut mucosa from Crohn's patients compared to healthy controls. In vitro, losartan suppresses expression of molecules related to fibrosis, fibroblast-to-myofibroblast differentiation, collagen deposition, and cytoskeletal alterations. In vivo, losartan decreases both inflammation and fibrosis in SAMP1/YitFc mice with established disease, and prevents reoccurrence of fibrosis following a novel relapse protocol.</p><p><strong>Conclusions: </strong>Losartan, and other drugs targeting the renin-angiotensin system, may serve as an effective treatment to successfully dampen intestinal fibrosis during active inflammation, as well as prevent its progression after corticosteroid-induced remission in Crohn's patients.</p>","PeriodicalId":94074,"journal":{"name":"Journal of Crohn's & colitis","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}