Transplant InternationalPub Date : 2024-11-07eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13477
Rupert Bright, Christoph F Mahler, Anamika Adwaney, Dhriti Dosani, Emma Morganti, Felix Friedl, Christian Nusshag, Claudius Speer, Louise Benning, Daniel Göth, Matthias Schaier, Claudia Sommerer, Markus Mieth, Arianeb Mehrabi, Martin Zeier, Christian Morath, Frank J M F Dor, Florian Kälble, Damien Ashby
{"title":"Adjusted Donor Age: A Clinical Score to Support Organ Acceptance Decisions in Deceased-Donor Kidney Transplantation.","authors":"Rupert Bright, Christoph F Mahler, Anamika Adwaney, Dhriti Dosani, Emma Morganti, Felix Friedl, Christian Nusshag, Claudius Speer, Louise Benning, Daniel Göth, Matthias Schaier, Claudia Sommerer, Markus Mieth, Arianeb Mehrabi, Martin Zeier, Christian Morath, Frank J M F Dor, Florian Kälble, Damien Ashby","doi":"10.3389/ti.2024.13477","DOIUrl":"10.3389/ti.2024.13477","url":null,"abstract":"<p><p>As transplant programmes have evolved to allow a wider donor pool, organ acceptance decisions have become increasingly complex and lack transparency and equality. Clinical scoring tools exist but there is limited consensus on their use. From a prospective observation of consecutive deceased-donor kidney offers in a large urban transplant centre, a simple score was developed based on donor age and other risk characteristics, excluding ischemia time and graft histology. The score was validated in subsequent cohorts of consecutive offers in the United Kingdom and Germany. In the development cohort of 389 kidney offers, 110 (28%) were transplanted and 175 (45%) declined. Nine risk factors were incorporated into a score based on age, but adjusted for the number of risk factors present, making an \"adjusted donor age,\" with offers separated into equal quintiles by decade. The score was validated in a UK cohort of 380 subsequent offers, and a German cohort of 431 offers. In both cohorts adjusted donor age discriminated between favourable and poor post-transplant outcomes (C-statistic 0.77 in the United Kingdom, 95% CI 0.65-0.88, and 0.71 in Germany, 95% CI 0.64-0.77). Adjusted donor age is a simple score quantifying deceased donor kidney quality, which is consistent with current practice and predicts post-transplant outcome.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13477"},"PeriodicalIF":2.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Vascular Reconstruction of Multiple Renal Arteries-A Risk Factor for Transplant Renal Artery Stenosis: Insight From a Matched Case-Control Study.","authors":"Devprakash Choudhary, Rajesh Vijayvergiya, Kamal Kishore, Vanji Nathan Subramani, Mohan Banoth, Sai Praneeth Reddy Perugu, Milind Mandwar, Bharat Bamaniya, Arun Panjathia, Parul Gupta, Shiva Kumar S Patil, Jasmine Sethi, Ujjwal Gorsi, Sarbpreet Singh, Deepesh Kenwar, Ashish Sharma","doi":"10.3389/ti.2024.13298","DOIUrl":"10.3389/ti.2024.13298","url":null,"abstract":"<p><p>Transplant Renal Artery Stenosis (TRAS) is the leading vascular complication following kidney transplantation (KT), causing premature allograft loss and increased post-KT mortality. While risk factors for TRAS, such as prolonged cold ischemia time and delayed graft function, are well-documented in deceased donor-KT, the risk factors remain less clearly defined in living donor-KT. This matched case-control study, conducted at a leading national transplant center predominantly performing living donor-KT, evaluated risk factors and long-term outcomes of clinical TRAS (cTRAS). cTRAS cases diagnosed from January 2009 to December 2022 were matched with four control kidney transplant recipients (KTRs) in a study powered to assess whether <i>ex-vivo</i> arterial vascular reconstruction of multiple renal arteries (VR-MRA) increases the risk of cTRAS. Among 2,454 KTs, 28 KTRs (1.14%) were diagnosed with cTRAS around 3.62 ± 1.04 months post-KT, with renal allograft dysfunction (92.86%) as the most common presenting feature. Notably, 27 cTRAS cases were successfully treated with endovascular intervention, yielding favorable outcomes over a 6-180 months follow-up period. The study identified <i>ex-vivo</i> VR-MRA as an independent risk factor for cTRAS (P < 0.001). cTRAS cases receiving timely treatment exhibited long-term outcomes in graft and patient survival similar to control KTRs. Early screening and timely intervention for cTRAS post-KT may improve graft and patient outcomes.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13298"},"PeriodicalIF":2.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-11-04eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13876
Johan Noble, Lara Cabezas, Aurelie Truffot, Lucile Dumolard, Thomas Jouve, Paolo Malvezzi, Lionel Rostaing, Céline Dard, Philippe Saas, Paolo Cravedi, Zuzana Macek-Jilkova
{"title":"Corrigendum: Glycolysis Changes in Alloreactive Memory B Cells in Highly Sensitized Kidney Transplant Recipients Undergoing Desensitization Therapy.","authors":"Johan Noble, Lara Cabezas, Aurelie Truffot, Lucile Dumolard, Thomas Jouve, Paolo Malvezzi, Lionel Rostaing, Céline Dard, Philippe Saas, Paolo Cravedi, Zuzana Macek-Jilkova","doi":"10.3389/ti.2024.13876","DOIUrl":"10.3389/ti.2024.13876","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/ti.2024.13029.].</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13876"},"PeriodicalIF":2.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11572526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-10-31eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13569
Marc Gjern Weiss, Anne Marye de Jong, Helene Seegert, Niels Moeslund, Hanno Maassen, Camilla Schjalm, Eline de Boer, Henri Leuvenink, Tom Eirik Mollnes, Marco Eijken, Anna Krarup Keller, Gerard Dijkstra, Bente Jespersen, Søren Erik Pischke
{"title":"Activation of the Innate Immune System in Brain-Dead Donors Can Be Reduced by Luminal Intestinal Preservation During Organ Procurement Surgery - A Porcine Model.","authors":"Marc Gjern Weiss, Anne Marye de Jong, Helene Seegert, Niels Moeslund, Hanno Maassen, Camilla Schjalm, Eline de Boer, Henri Leuvenink, Tom Eirik Mollnes, Marco Eijken, Anna Krarup Keller, Gerard Dijkstra, Bente Jespersen, Søren Erik Pischke","doi":"10.3389/ti.2024.13569","DOIUrl":"10.3389/ti.2024.13569","url":null,"abstract":"<p><p>Organs obtained from brain dead donors can have suboptimal outcomes. Activation of the innate immune system and translocation of intestinal bacteria could be causative. Thirty two pigs were assigned to control, brain death (BD), BD + luminal intestinal polyethylene glycol (PEG), and BD + luminal intestinal University of Wisconsin solution (UW) groups. Animals were observed for 360 min after BD before organ retrieval. 2,000 mL luminal intestinal preservation solution was instilled into the duodenum at the start of organ procurement. Repeated measurements of plasma C3a, Terminal Complement Complex (TCC), IL-8, TNF, and lipopolysaccharide binding protein were analysed by immunoassays. C3a was significantly higher in the BD groups compared to controls at 480 min after brain death. TCC was significantly higher in BD and BD + UW, but not BD + PEG, compared to controls at 480 min. TNF was significantly higher in the BD group compared to all other groups at 480 min. LPS binding protein increased following BD in all groups except BD + PEG, which at 480 min was significantly lower compared with all other groups. Brain death induced innate immune system activation was decreased by luminal preservation using PEG during organ procurement, possibly due to reduced bacterial translocation.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13569"},"PeriodicalIF":2.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560447/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-10-31eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13641
Marianna Maspero, Carlo Sposito, Marco A Bongini, Tommaso Cascella, Maria Flores, Marco Maccauro, Carlo Chiesa, Monica Niger, Filippo Pietrantonio, Giuseppe Leoncini, Valentina Bellia, Sherrie Bhoori, Vincenzo Mazzaferro
{"title":"Liver Transplantation for Intrahepatic Cholangiocarcinoma After Chemotherapy and Radioembolization: An Intention-To-Treat Study.","authors":"Marianna Maspero, Carlo Sposito, Marco A Bongini, Tommaso Cascella, Maria Flores, Marco Maccauro, Carlo Chiesa, Monica Niger, Filippo Pietrantonio, Giuseppe Leoncini, Valentina Bellia, Sherrie Bhoori, Vincenzo Mazzaferro","doi":"10.3389/ti.2024.13641","DOIUrl":"10.3389/ti.2024.13641","url":null,"abstract":"<p><p>Liver transplantation (LT) is a potentially curative experimental treatment for unresectable intrahepatic cholangiocarcinoma (iCC). Pre-transplant downstaging may help defining tumor aggressiveness and drive patient selection. We report the preliminary results of LT for liver-limited unresectable iCC after sequential downstaging with systemic chemotherapy and radioembolization (SYS-TARE). In case of sustained disease stability after SYS-TARE, patients underwent surgical nodal sampling and, if negative, were listed for LT. In this study, 13 patients with unresectable iCC underwent downstaging with SYS-TARE. The median age was 70 years and 77% were female. All had single bulky lesions at diagnosis. After SYS-TARE, 9 (69%) dropped out: 3 due to progressive disease after TARE with no response to second-line, 4 due to extrahepatic disease development and 2 due to positive nodal disease at pre-listing abdominal exploration. The median OS after dropout was 11.5 months. Four (31%) were successfully listed and transplanted. At pathology, viable tumor ranged from 30% to less than 5%. All four patients are alive and disease-free at 73, 40, 12, and 8 months from LT. LT for unresectable iCC after downstaging with SYS-TARE appears to select suitable patients for LT, achieving optimal oncological outcomes in case of response to therapy and no lymphnodal spread.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13641"},"PeriodicalIF":2.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-10-31eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13873
Hans H Hirsch, Camille N Kotton
{"title":"A Hitchhiker's Guide to the BK Galaxy.","authors":"Hans H Hirsch, Camille N Kotton","doi":"10.3389/ti.2024.13873","DOIUrl":"10.3389/ti.2024.13873","url":null,"abstract":"","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13873"},"PeriodicalIF":2.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142636107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-10-30eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13551
Mario Fernández-Ruiz, Tamara Ruiz-Merlo, Isabel Rodríguez-Goncer, José María Caso, Francisco López-Medrano, Patricia Parra, Rafael San Juan, Natalia Polanco, Esther González, Amado Andrés, José María Aguado, Natalia Redondo
{"title":"Performance of a Global Functional Assay Based on Interferon-γ Release to Predict Infectious Complications and Cancer After Kidney Transplantation.","authors":"Mario Fernández-Ruiz, Tamara Ruiz-Merlo, Isabel Rodríguez-Goncer, José María Caso, Francisco López-Medrano, Patricia Parra, Rafael San Juan, Natalia Polanco, Esther González, Amado Andrés, José María Aguado, Natalia Redondo","doi":"10.3389/ti.2024.13551","DOIUrl":"10.3389/ti.2024.13551","url":null,"abstract":"<p><p>The QuantiFERON-Monitor assay (QTF-Monitor) is intended to assess innate and adaptive immune responses by quantifying interferon (IFN)-γ release upon whole blood stimulation with a TLR7/8 agonist and an anti-CD3 antibody. We performed the QTF-Monitor in 126 kidney transplant recipients (KTRs) at different points during the first 6 post-transplant months. The primary outcome was overall infection, whereas secondary outcomes included bacterial infection, opportunistic infection and <i>de novo</i> cancer. The association between IFN-γ production and outcomes was analyzed as \"low\" immune responses (<15 IU/mL) and as a continuous variable to explore alternative thresholds. There were no significant differences in the occurrence of overall infection according to the QTF-Monitor at any monitoring point. Regarding secondary outcomes, KTRs with a low response at week 2 experienced a higher incidence of bacterial infection (50.8% versus 24.4%; <i>P</i>-value = 0.006). Low response at month 1 was also associated with opportunistic infection (31.6% versus 14.3%; <i>P</i>-value = 0.033). The discriminative capacity of IFN-γ levels was poor (areas under the ROC curve: 0.677 and 0.659, respectively). No differences were observed for the remaining points or post-transplant cancer. In conclusion, the QTF-Monitor may have a role to predict bacterial and opportunistic infection in KTRs when performed early after transplantation.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13551"},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11557340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-10-30eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.12822
Xin Jin, Jacques Pirenne, Robin Vos, Charlotte Hooft, Janne Kaes, Jan Van Slambrouck, Phéline Kortleven, Christelle Vandervelde, Hanne Beeckmans, Pieterjan Kerckhof, Marianne S Carlon, Dirk Van Raemdonck, Mark R Looney, Bart M Vanaudenaerde, Laurens J Ceulemans
{"title":"Donor-Specific Blood Transfusion in Lung Transplantation.","authors":"Xin Jin, Jacques Pirenne, Robin Vos, Charlotte Hooft, Janne Kaes, Jan Van Slambrouck, Phéline Kortleven, Christelle Vandervelde, Hanne Beeckmans, Pieterjan Kerckhof, Marianne S Carlon, Dirk Van Raemdonck, Mark R Looney, Bart M Vanaudenaerde, Laurens J Ceulemans","doi":"10.3389/ti.2024.12822","DOIUrl":"10.3389/ti.2024.12822","url":null,"abstract":"<p><p>Lung transplantation is still hindered by a high rate of chronic rejection necessitating profound immunosuppression with its associated complications. Donor-specific blood transfusion is a pre-transplant strategy aimed at improving graft acceptance. In contrast with standard stored blood or donor-specific regulatory T cells transfusions, this approach utilizes fresh whole blood from the donor prior to allograft transplantation, encompassing all cell types and plasma. The precise mechanisms underlying donor-specific blood transfusion-induced tolerance remain incompletely understood. Associations with regulatory/helper T cells, modulation of mononuclear phagocytic cells or microchimerism have been suggested. While numerous (pre-)clinical studies have explored its application in solid organ transplants like liver, kidney, and intestine, limited attention has been given to the setting of lung transplantation. This comprehensive review summarizes existing knowledge on the mechanisms and outcomes of donor-specific blood transfusion in solid organ transplants both in preclinical and clinical settings. We also address the potential benefits and risks associated with donor-specific blood transfusion in the field of lung transplantation, offering insights into future research directions.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"12822"},"PeriodicalIF":2.7,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transplant InternationalPub Date : 2024-10-25eCollection Date: 2024-01-01DOI: 10.3389/ti.2024.13313
Min Seo Ki, Nam Eun Kim, Ala Woo, Song Yee Kim, Young Sam Kim, Ha Eun Kim, Jin Gu Lee, Hyo Chae Paik, Moo Suk Park
{"title":"Post-Transplant Vitamin D Deficiency in Lung Transplant Recipients: Impact on Outcomes and Prognosis.","authors":"Min Seo Ki, Nam Eun Kim, Ala Woo, Song Yee Kim, Young Sam Kim, Ha Eun Kim, Jin Gu Lee, Hyo Chae Paik, Moo Suk Park","doi":"10.3389/ti.2024.13313","DOIUrl":"10.3389/ti.2024.13313","url":null,"abstract":"<p><p>Despite the recognized clinical significance of vitamin D deficiency in other solid organ transplant recipients, its specific relevance in lung transplantation remains to be fully understood. In this study, we performed a retrospective observational study on the impact of vitamin D deficiency on clinical outcomes and prognosis in 125 lung transplant recipients (LTRs) from October 2014 to March 2020 at a university hospital in Seoul, South Korea. Among 125 LTRs, 51 patients (40.8%) were vitamin D deficient. LTRs in the vitamin D-deficient group exhibited a higher incidence of post-transplant pneumonia and overall mortality than those with normal vitamin D levels during the follow-up period. This trend persisted when subjects were stratified into vitamin D tertiles. Furthermore, post-transplant vitamin D levels and C-reactive protein (CRP) significantly impacted pneumonia incidence and survival outcomes. Prognosis also varied based on cumulative vitamin D supplementation after transplantation, with patients receiving higher cumulative supplementation demonstrating improved prognosis. Our findings underscore the importance of assessing and maintaining optimal vitamin D levels post-transplantation, suggesting a potential avenue for improving outcomes in lung transplant recipients, especially in mitigating infection risk and enhancing long-term survival. Further research into optimal vitamin D levels and supplementation strategies in this population is warranted.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13313"},"PeriodicalIF":2.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessment of the Therapeutic Potential of Enhancer of Zeste Homolog 2 Inhibition in a Murine Model of Bronchiolitis Obliterans Syndrome.","authors":"Kyoto Matsudo, Shinkichi Takamori, Tomoyoshi Takenaka, Mototsugu Shimokawa, Asato Hashinokuchi, Taichi Nagano, Fumihiko Kinoshita, Takaki Akamine, Mikihiro Kohno, Gouji Toyokawa, Tomoharu Yoshizumi","doi":"10.3389/ti.2024.13227","DOIUrl":"https://doi.org/10.3389/ti.2024.13227","url":null,"abstract":"<p><p>Bronchiolitis obliterans syndrome (BOS) is a chronic complication following lung transplantation that limits the long-term survival. Although the enhancer of zeste homolog 2 (EZH2) is involved in post-transplantation rejection, its involvement in BOS pathogenesis remains unclear. We aimed to investigate the therapeutic potential of EZH2 inhibition in BOS. 3-deazaneplanocin A (DZNep) was administered intraperitoneally to heterotopic tracheal transplant recipient model mice. Tracheal allografts were obtained on days 7, 14, 21, and 28 after transplantation. The obstruction ratios of the DZNep and control groups on days 7, 14, 21, and 28 were 15.1% ± 0.8% vs. 20.4% ± 3.6% (<i>p</i> = 0.996), 16.9% ± 2.1% vs. 67.7% ± 11.5% (<i>p</i> < 0.001), 47.8% ± 7.8% vs. 92.2% ± 5.4% (<i>p</i> < 0.001), and 60.0% ± 9.6% vs. 95.0% ± 2.3% (<i>p</i> < 0.001), respectively. The levels of interleukin (IL)-6 and interferon-γ on day 7 and those of IL-2, tumor necrosis factor, and IL-17A on days 14, 21, and 28 were significantly reduced following DZNep treatment. DZNep significantly decreased the number of infiltrating T-cells on day 14. In conclusion, DZNep-mediated EZH2 inhibition suppressed the inflammatory reactions driven by pro-inflammatory cytokines and T cell infiltration, thereby alleviating BOS symptoms.</p>","PeriodicalId":23343,"journal":{"name":"Transplant International","volume":"37 ","pages":"13227"},"PeriodicalIF":2.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11543400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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