Transplantation最新文献

{"title":"Split Tolerance in Intestinal Transplantation: Promising Translational Evidence With Relevance for Daily Clinical Practice.","authors":"Gabriel E Gondolesi, Alexander Kroemer, Martin Rumbo","doi":"10.1097/TP.0000000000005409","DOIUrl":"10.1097/TP.0000000000005409","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e422-e423"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Belgian Consensus Guidelines Within Eurotransplant on Imlifidase-enabled Deceased Donor Kidney Transplantation in Highly Sensitized Patients.","authors":"Dirk R J Kuypers, Frans H J Claas, Antoine Bouquegneau, Antoine Buemi, Johan W de Fijter, Marie-Paule Emonds, Giuseppe Gambino, Thibaut Gervais, André Gothot, Vanda Holovska, Alain Le Moine, Annick Massart, Dimitri Mikhalski, Maarten Naesens, Lissa Pipeleers, Justine Schmitt, Corentin Streel, Steven Van Laecke, Laurent Weekers, Karl Martin Wissing, Nada Kanaan","doi":"10.1097/TP.0000000000005388","DOIUrl":"10.1097/TP.0000000000005388","url":null,"abstract":"<p><p>Highly sensitized (HS) kidney transplant (KTx) candidates, that is, typically considered internationally as those with panel-reactive antibody levels of >85%, remain a substantial subpopulation of patients with low chance of receiving a compatible organ. Among its many objectives, Eurotransplant-an international transplant organ allocation network serving 8 European countries-aims to improve the management of HS KTx candidates through its prioritized \"acceptable mismatch\" (AM) program. However, despite this program, some HS patients within the Eurotransplant network who have panel-reactive antibodies >85% still cannot access donor kidneys. For patients who remain in the AM program for ≥3 y without undergoing transplantation, an additional prioritization strategy has been implemented. This involves defining further AMs to allow for desensitization with imlifidase within the AM program. While the AM desensitization program was being developed, the Belgian Imlifidase Scientific Expert Group within the Eurotransplant network independently recognized the need for guidelines on imlifidase desensitization for real-world use in HS KTx candidates (including both AM and Eurotransplant Kidney Allocation System patients). This article describes the consensus guidelines they subsequently developed, which represent a model that any center within the Eurotransplant region could adapt or apply in clinical practice when treating HS KTx candidates who require imlifidase desensitization. The consensus guidelines include patient eligibility criteria for imlifidase treatment that align with Eurotransplant allocation rules and incorporate posttransplant management strategies for HS patients. These guidelines are dynamic and will be reviewed and updated regularly as Eurotransplant rules change and imlifidase experience grows.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1274-1283"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Equity in Access to Kidney Transplantation: Policy Change Is Necessary But Not Enough.","authors":"Joy E Obayemi, Dinee C Simpson","doi":"10.1097/TP.0000000000005425","DOIUrl":"10.1097/TP.0000000000005425","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1292-1293"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inactivating the Innate Immune Receptor CD11b With a First-in-class Monoclonal Antibody Prolongs the Survival of Kidney Allografts in Nonhuman Primates.","authors":"Abbas Dehnadi, Ivy A Rosales, Jian-Ping Xiong, Tatsuo Kawai, Hyshem H Lancia, Gilles Benichou, Robert B Colvin, A Benedict Cosimi, M Amin Arnaout","doi":"10.1097/TP.0000000000005370","DOIUrl":"10.1097/TP.0000000000005370","url":null,"abstract":"<p><strong>Backgournd: </strong>Peritransplant ischemia/reperfusion injury (IRI) plays a central pathogenic role in nondelayed or delayed kidney allograft function immediately after transplantation and increases the risk of subsequent rejection. Potential therapies targeting specific cytokines or complement proteins to limit IRI have failed in clinical trials. Monoclonal antibody 107 (mAb107), a \"pure\" (nonactivating) inhibitor of the archetypal innate immune receptor integrin CD11b, has been shown to extend the survival of IRI nonhuman primate native kidneys in an in situ model.</p><p><strong>Methods: </strong>Here, we administered mAb107 before allograft revascularization to determine its efficacy for extending the survival of ischemia-damaged donor kidneys transplanted into major histocompatibility complex-mismatched nonhuman primate recipients.</p><p><strong>Results: </strong>We observed a significant delay in the onset of rejection and prolongation of allograft survival in mAb107-treated versus control recipients. Early allograft biopsies suggest this is secondary to the selective suppression of infiltrating neutrophils and macrophages.</p><p><strong>Conclusions: </strong>These observations support the hypothesis that inactivating CD11b with mAb107 may provide an effective strategy for prolonging the survival of ischemia-damaged allografts and increasing the successful use of marginal donor organs.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1350-1356"},"PeriodicalIF":5.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12289432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TDO2 Deficiency Exacerbates the Immune Rejection Response in Rat Liver Transplantation via the Kyn-AHR Axis.","authors":"Shanbao Li, Lei Li, Junyong Weng, Zeping He, Jing Lu, Wanyue Cao, Fangbin Song, Zhonglin Zhu, Bingjie Guan, Jinyan Zhang, Junming Xu","doi":"10.1097/TP.0000000000005386","DOIUrl":"10.1097/TP.0000000000005386","url":null,"abstract":"<p><strong>Background: </strong>The role of tryptophan 2,3-dioxygenase2 (TDO2), a key enzyme in the L-tryptophan (Trp)-kynurenine (Kyn) pathway, in liver transplant immunity is unclear. This study aims to explore the role of TDO2 in liver transplant rejection.</p><p><strong>Methods: </strong>We used clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 to construct a TDO2 knockout rat model for liver transplant rejection. We validated the effects of TDO2 on acute rejection and survival, assessed TDO2 expression, and measured Trp and Kyn levels. We studied how TDO2 deficiency affects inflammatory cytokines, analyzed immune cell subtypes and their spatial distribution, and examined programmed death 1 and programmed cell death-ligand 1 (PDL1) spatial distribution and expression using multiplex immunohistochemistry. We also validated the regulatory mechanism of TDO2 on transplant-related immune cells in vivo and in vitro.</p><p><strong>Results: </strong>TDO2 deficiency in the allograft liver worsens acute rejection and reduces survival rates. During transplant rejection, TDO2 expression increases, enhancing Trp metabolism and elevating serum Kyn levels. TDO2 knockout mitigates this process. The TDO2-Kyn-aryl hydrocarbon receptor pathway regulates acute rejection. TDO2 knockout reprograms immune cell distribution, decreasing regulatory T cells and M2 macrophages in the intermediate region while increasing CD8 + T cells and M1 macrophages in the portal area, leading to M1 polarization. Additionally, TDO2 deficiency raises programmed death 1 and programmed cell death-ligand 1 expression, varying with the spatial distribution and quantity of immune cells. TDO2 can regulate the proliferation and differentiation of various immune cells through the Kyn-aryl hydrocarbon receptor pathway.</p><p><strong>Conclusions: </strong>Collectively, we elucidated the mechanism of TDO2 in liver transplant immune rejection and used spatial immunity to reveal the impact of TDO2 on liver transplantation.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e386-e399"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"International Xenotransplantation Association (IXA) Position Paper on Kidney Xenotransplantation.","authors":"Raphael P H Meier, Richard N Pierson, Jay A Fishman, Leo H Buhler, Rita Bottino, Joseph M Ladowski, Burcin Ekser, Eckhard Wolf, Paolo Brenner, Francesco Ierino, Muhammad Mohiuddin, David K C Cooper, Wayne J Hawthorne","doi":"10.1097/TP.0000000000005372","DOIUrl":"10.1097/TP.0000000000005372","url":null,"abstract":"<p><p>Porcine kidney xenotransplantation for end-stage renal disease (ESRD) has reached the stage of clinical testing following major advances in donor pig genetic modifications and effective immunosuppressive strategies through decades of rigorous translational research. Reports of pig kidney xenograft survival beyond 1 year post-transplant in nonhuman primate (NHP) models justify optimism for its potential as an alternative to allotransplantation. In the United States, experimental transplantations of genetically engineered (GE) porcine kidneys into brain-dead subjects and a small number of ESRD patients have shown no evidence of hyperacute rejection and adequate pig kidney function for up to several months. Here we discuss pre-clinical/clinical results, infectious disease, ethical, and regulatory considerations, and propose evidence-based recommendations. For initial clinical trials in kidney xenotransplantation, we make the following recommendations: (i) transplantation with organs from a triple knockout (TKO) donor pig, preferably with added human transgenes, (ii) an immunosuppressive regimen with induction therapy to deplete T (and possibly B) cells, and maintenance therapy based on a cluster of differentiation (CD)40/CD154 co-stimulation pathway blockade, (iii) the patient should be fully acceptable as a candidate for allotransplantation but should be unlikely ever to receive an allograft. Patients aged 60-69 years (extendable to 40-75 years, if one of the criteria mentioned below is present), of blood group B or O, and with diabetes are most at risk in this regard. Other patients who could be considered are (i) those who have lost two or more previous kidney allografts from recurrent disease in the graft, (ii) those with broad human leukocyte antigen (HLA)-reactivity but no evidence of anti-pig antibodies, including swine leukocyte antigen (SLA), and (iii) those with failing vascular access. Clinical pilot studies in carefully and highly selected patients with no alternative therapy will provide the foundation upon which to base subsequent formal expanded clinical trials.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1313-1328"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Unified Metric of Human Immune Health?","authors":"Tarrion Baird, Stephen N Sansom","doi":"10.1097/TP.0000000000005378","DOIUrl":"10.1097/TP.0000000000005378","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1269-1270"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined Pancreas-kidney Transplantation After Rescue Allocation: The Eurotransplant Experience: A Retrospective Multicenter Outcome Analysis.","authors":"Volker Assfalg, Felix Stocker, Norbert Hüser, Daniel Hartmann, Edouard Matevossian, Milou van Bruchem, Serge Vogelaar, Lutz Renders, Christoph Schmaderer, Christian Margreiter, Andras Deak, Franka Messner, Michael Kammer, Dirk Ysebaert, Daniel Jacobs-Tulleneers-Thevissen, Dimitri Mikhalski, Steven van Laecke, Pieter Gillard, Andreas Kahl, Richard Viebahn, Carina Riediger, Bernd Jänigen, Moritz Schmelzle, Friedrich Alexander von Samson-Himmelstjerna, Dirk Stippel, Ana Harth, Martin Nitschke, Dionysios Koliogiannis, Andreas Pascher, Joachim Hoyer, Julia Weinmann-Menke, Mario Schiffer, Sebastian Hinz, Silvio Nadalin, Kai Lopau, Volkert Huurman, Miha Arnol, Gregor Miller","doi":"10.1097/TP.0000000000005354","DOIUrl":"10.1097/TP.0000000000005354","url":null,"abstract":"<p><strong>Background: </strong>Simultaneous pancreas-kidney transplantation (SPKT) is the therapy of choice for selected patients with complicated type 1 diabetes mellitus and end-stage renal disease. Pancreas rescue allocation was implemented in Eurotransplant allocation algorithms to increase organ utilization, concurrently facilitating transplantation of supposedly inferior quality organs. The aim of this study was to examine whether outcomes of SPKT after rescue allocation, which can either be recipient-oriented extended allocation or competitive rescue allocation, were as good as after standard allocation.</p><p><strong>Methods: </strong>This retrospective multicenter analysis of 1504 SPKT performed from 2013 to 2021 evaluated outcomes by allocation type considering survival of patients, pancreas grafts, and kidney grafts. Multivariable analyses further explored the influence of specific donor-, recipient-, and transplant-related variables on outcomes.</p><p><strong>Results: </strong>Multivariable analyses showed no significant differences in SPKT outcome for standard allocation versus either rescue allocation type regarding patient, pancreas graft, and kidney graft survival. Rescue allocation organ donors were older, had higher body mass index, and were more likely to smoke. Rescue allocation had fewer HLA matches. Cold ischemic times of both pancreas and kidneys were longer in competitive rescue allocation but not in recipient-oriented extended allocation. Rescue allocation pancreas recipients had shorter waiting times. Multivariable analyses showed inferior pancreas and kidney graft survival for higher donor age. Higher recipient age correlated with higher mortality despite better pancreas graft survival.</p><p><strong>Conclusions: </strong>SPKT outcome after rescue allocation is comparable with standard allocation in both patient and graft survival. Age of both donors and recipients essentially influences the success of SPKT.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1437-1448"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of Non-HLA Autoantibodies in Predicting Graft Survival After Heart Transplantation.","authors":"Gyu Chul Oh, Jong-Chan Youn, Hyun-Jai Cho, Jeehoon Kang, Eun-Seok Jeon, Jin-Oh Choi, Sung-Ho Jung, Jaewon Oh, Seok-Min Kang, Myoung Soo Kim, Jae-Joong Kim, Hae-Young Lee, Eun Young Song","doi":"10.1097/TP.0000000000005368","DOIUrl":"10.1097/TP.0000000000005368","url":null,"abstract":"<p><strong>Background: </strong>The presence of antibodies to donor-specific HLAs is a well-known risk factor associated with heart transplantation (HTx) outcomes. Recently, non-HLA antibodies were reported to be associated with HTx outcomes.</p><p><strong>Methods: </strong>We evaluated the association between the presence of non-HLA antibodies with early (≤1 y) and long-term graft failure in 192 patients undergoing HTx in 4 large transplant centers in Korea.</p><p><strong>Results: </strong>Antibodies to vimentin (AVA) and type II collagen (ACA) were associated with a lower rate of 1-y graft survival (78.6% versus 92.6%, log-rank P  = 0.006 for AVA + ; 72.2% versus 91.1%, log-rank P  = 0.015 for ACA + ). AVA + stratified 1-y graft survival in patients with donor-specific antibodies (DSAs + ; 45.5% versus 94.1%, log-rank P  = 0.002). AVA + also improved the prediction models based on conventional risk factors derived from Cox regression analysis (integrated discrimination improvement, 9%; P  < 0.001; net reclassification index, 24%; P  = 0.047). Compared with AVA - /ACA - patients, AVA + /ACA + patients had poor graft survival both in the early and late periods (all log-rank P  < 0.001).</p><p><strong>Conclusions: </strong>In conclusion, the presence of non-HLA antibodies to vimentin and type II collagen was associated with poor graft outcomes in patients undergoing HTx. These findings highlight the need to consider non-HLA antibodies in assessing transplant recipients and tailoring immune modulation strategies.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1449-1457"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining an NK Cell-enriched Rejection-like Phenotype in Liver Transplant Biopsies From the INTERLIVER Study.","authors":"Katelynn S Madill-Thomsen, Patrick T Gauthier, Marwan Abouljoud, Chandra Bhati, David Bruno, Michał Ciszek, Magdalena Durlik, Sandy Feng, Bartosz Foroncewicz, Michał Grąt, Krzysztof Jurczyk, Josh Levitsky, Geoff McCaughan, Daniel Maluf, Aldo Montano-Loza, Dilip Moonka, Krzysztof Mucha, Marek Myślak, Agnieszka Perkowska-Ptasińska, Grzegorz Piecha, Trevor Reichman, Olga Tronina, Marta Wawrzynowicz-Syczewska, Samir Zeair, Philip F Halloran","doi":"10.1097/TP.0000000000005269","DOIUrl":"10.1097/TP.0000000000005269","url":null,"abstract":"<p><strong>Background: </strong>Initial analysis of liver transplant biopsies in the INTERLIVER study ( ClinicalTrials.gov ; unique identifier NCT03193151) using rejection-associated transcripts failed to find an antibody-mediated rejection state (ie, rich in natural killer [NK] cells and with interferon-gamma effects). We recently developed an optimization strategy in lung transplants that isolated an NK cell-enriched rejection-like (NKRL) state that was molecularly distinct from T cell-mediated rejection (TCMR). Here we apply the same strategy to a liver transplant biopsy population.</p><p><strong>Methods: </strong>We used this strategy to search for a molecular NKRL state in 765 consented liver transplant biopsies collected at participating international centers for gold-standard histology and molecular assessment by genome-wide microarrays. Validation through a training set-test set approach of an optimized selection of variables as inputs into unsupervised rejection classification identified an NKRL state in livers.</p><p><strong>Results: </strong>The full model classified 765 biopsies into the following molecular phenotypes, characterized by their gene expression: no-rejection 54%, TCMR 16%, NKRL 13%, and injury 16%. Top TCMR transcripts were expressed in effector T cells; top NKRL transcripts were almost exclusively expressed in NK cells; and both had increased interferon-γ-inducible transcripts, which were more pronounced in TCMR. Most TCMR biopsies had significant parenchymal injury, molecular fibrosis, and abnormal biochemistry. NKRL biopsies had no excess of injury, fibrosis, or biochemistry abnormalities.</p><p><strong>Conclusions: </strong>Optimized rejection algorithms indicate that some liver transplants manifest an NKRL state that is well tolerated in the short term postbiopsy and with minimal injury and relatively normal biochemistry, while also underscoring the potential of TCMR to produce extensive parenchymal injury.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"1367-1382"},"PeriodicalIF":5.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}