American Journal of Transplantation最新文献

{"title":"Continued Optimism for the use of Imlifidase for Desensitization in Kidney Transplant.","authors":"Carrie A Schinstock,Mark Stegall","doi":"10.1016/j.ajt.2025.05.015","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.015","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"128 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065584","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":"Unraveling CD8+ T Cell Alloimmunity: Insights into the Direct Pathway of Antigen Recognition from Modern Experimental Tools.","authors":"Joel S Freibaum,Riley P Leathem,William Braaton,Scott M Krummey","doi":"10.1016/j.ajt.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.009","url":null,"abstract":"Early experimental investigations of alloimmunity demonstrated that the T cell response against allogeneic antigens is robust and results from a high precursor frequency of responding clones. Seminal studies using cell culture-based methods led to an overall model in which CD8+ T cells are able to recognize self-peptide complexed to allogeneic peptide MHC, termed the direct allogeneic antigen recognition pathway. Recently, three groups used modern experimental approaches, including MHC class I tetramers, to further investigate the nature of direct allogeneic antigen recognition by CD8+ T cells in mice and humans. In a model of liver-induced transplant tolerance, Son et al showed that the MHC class I alloimmune CD8+ T cell response is peptide dependent. Cohen et al elucidated the H-Ld QL9 allogeneic epitope and showed that reactive CD8+ T cells were peptide discriminating. Zhang et al engineered artificial antigen presenting cells to show that human alloreactive CD8+ T cells against HLA-A antigens were MHC restricted, and demonstrated a public HLA-A2 CD8+ T cell response in four donors. Through new experimental tools, these studies offer granular evidence of the mechanisms by which CD8+ T cells recognize allogeneic antigen, and provide a framework for future approaches to selectively target them.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"28 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065586","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":"Recommendations to Overcome Barriers to Transplant Fellowship Training: A Report from the American Society of Transplantation Fellows Task Force.","authors":"Jon Kobashigawa,Josh Levitsky,Neeraj Singh,Kiran Khush,Sean Pinney,Elizabeth Aby,Aasim Afzal,Deborah Adey,Anshul Bhalla,Mona Doshi,Samira Farouk,Alyson Fox,Shelley Hall,Michelle Kittleson,Lindsay King,Alexander Kuo,Deborah Levine,Yosef Manla,Jamak Modaresi,Arjmand Mufti,Prince Mohan Anand,Michael Nurok,Jp Norvell,Neehar Parikh,Anjana Pillai,Faruq Pradhan,Allison Ramsey,Milagros Samaniego-Picota,Ishna Poojary-Hohman,Manpreet Samra,Deirdre Sawinski,Kelly Schlendorf,Stuart Sweet,Bekir Tanriover,Sarthak Virmani,Roy D Bloom","doi":"10.1016/j.ajt.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.007","url":null,"abstract":"With the expansion of solid organ transplantation activities in the US, there is a critical need for more transplant care providers and trainees to sustain and advance the field of transplantation. However, there has been a pending shortage of trainees pursuing transplant fellowship training in the U.S. in recent years. To address this issue, the American Society of Transplantation (AST) organized the Fellows' Task Force, including representatives of all four major organs from various AST communities of practice, to understand the drivers of this pending shortage and develop strategies to increase interest in transplant specialization. The task force identified four areas of focus, including early & sustained exposure to transplant medicine, awareness through education, flexible fellowships & pathways to transplant, and work/life resources. Based on these focus areas, the task force developed recommendations and action items, which were compiled into a report to be implemented by individuals, institutions, communities of practice (work groups), and societies such as the AST. We hope that this report will be the first step in overcoming barriers and concerns to encourage the pursuit of specialization in transplantation in the US.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"15 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065874","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":"Donor-specific Mesenchymal Stem Cell Infusion in Human and Non-human Primate Kidney Transplantation.","authors":"Imran J Anwar,Shu Li,Michael Mulvihill,Robin Schmitz,Brian Shaw,Qimeng Gao,Sherri Swan-Nesbit,Lynn A Cheatham,Tam How,Allison Miller,Kyha Williams,Fang-Fang Yin,William Giles,Joanne Kurtzberg,Sindhu Chandran,Nancy Bridges,Lyudmila Lyakh,Cynthia Breeden,Krupa Gandhi,Michelle Sever,Mingqing Song,He Xu,Allan D Kirk","doi":"10.1016/j.ajt.2025.05.008","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.008","url":null,"abstract":"We report the results of two independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell (MSC) infusions in inducing immune-tolerance in nonhuman primate (NHP) and human kidney transplant recipients treated with depletional induction and belatacept/sirolimus maintenance. Fifteen NHPs received rhesus ATG induction and were divided in three groups: control (n=6), pre-transplant thymic irradiation (TI, n=4), and TI with monthly donor-MSC infusion (n=5). Sirolimus was discontinued at day-180, and belatacept at day-365 post-transplantation. In humans, six patients enrolled in ITN062ST underwent transplantation with alemtuzumab induction; four received 12 monthly donor-MSC infusions followed by immunosuppression withdrawal (ISW) if eligible. Donor-MSC infusion was acutely well-tolerated in humans and NHPs. Chimerism was not established, and tolerance was not induced in either study. Two of five NHPs that received MSCs rejected while on belatacept monotherapy with detectable donor-specific antibody (DSA). Two patients did not initiate ISW due to de novo DSA and borderline rejection, and two patients failed ISW due to reversible rejection. In conclusion, donor-MSCs can be given to NHPs or humans repeatedly without acute consequences, but they neither lead to detectable chimerism nor induce tolerance. In a subset of recipients, infused MSCs can be sensitizing. Trial Registration. ClinicalTrials.gov - NCT03504241.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"29 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982455","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":"Beyond the HOPE Act: Roadmap to Expanding Kidney and Liver Transplants for People with Human Immunodeficiency Virus Utilizing Grafts from Donors with Human Immunodeficiency Virus.","authors":"Tzu-Hao Lee,Kara Wegermann,Ken Sutha,George Cholankeril,Chia-Yu Chu,Nhu Thao Nguyen Galvan,Abbas Rana,John A Goss,Tyler Lambing,Felice Cinque,Giada Sebastiani,Keyur Patel,Susanna Naggie,Cameron R Wolfe","doi":"10.1016/j.ajt.2025.05.013","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.013","url":null,"abstract":"People living with HIV (PWH) face limited access to organ transplantation despite higher rates of end-organ disease. The HIV Organ Policy Equity (HOPE) Act, enacted in 2015, allowed transplants from donors with HIV to recipients with HIV (HIV D+/R+) under research protocols. Studies have since demonstrated overall comparable outcomes between HIV D+/R+ and HIV D-/R+ transplants, leading to the removal of the research requirement for HIV D+/R+ kidney and liver transplants in November 2024. However, some remaining medical concerns and systemic barriers still need to be addressed, especially for centers that did not participate in the HOPE Act. This manuscript reviews the history, evidence, and key considerations for HIV D+/R+ kidney and liver transplants. Furthermore, a roadmap for implementation, emphasizing the need for reviewing local regulations, establishing multidisciplinary teams, developing personalized protocols, providing medical and culture training, engaging organ procurement organizations and local PWH community, and continuing data collection and quality improvement, is discussed. The removal of research restrictions offers a critical opportunity to reduce disparities in transplant access for PWH. Transplant providers should embrace this opportunity to expand access while continuing to address the remaining medical and systemic challenges to ensure that more PWH receive life-saving transplants.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"5 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982456","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":"The Short End of the Stick: Access to Lung Transplantation for Short-Statured Patients in the Composite Allocation Score Era.","authors":"Isaac S Alderete,Alexandria L Soto,Samantha E Halpern,Arya Pontula Bsph,Ewout Muylle,Kentaro Nakata,Kunal J Patel,Jacob Klapper,Matthew G Hartwig","doi":"10.1016/j.ajt.2025.05.011","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.011","url":null,"abstract":"Short-statured lung transplant (LTx) candidates experience longer waitlist times than taller ones. The new Composite Allocation Score (CAS) includes height to enhance allocation equity. We assessed the impact of CAS on waitlist outcomes for different height groups. We queried a national transplant database for LTx candidates listed from 2021 to 2024, categorized into four height groups: ≤162 cm, 162-170 cm, 170-176.5 cm, >176.5 cm. Competing risk and Cox regression models assessed the impact of height on waitlist outcomes, including an interaction term between height and allocation era to assess effect modification. Of the 9,383 candidates identified, those >176.5 cm had an increased likelihood of transplantation (sHR 1.15) compared to the 170-176.5 cm group, while those ≤162 cm had a lower likelihood (sHR 0.70). The overall likelihood of transplantation was higher in the CAS era (sHR 1.17); The interaction term for height ≤162 cm and CAS era was significant (sHR 1.15), suggesting a modest improvement in access for this group under CAS. Further, candidates ≤162 cm experienced a higher hazard of mortality in the CAS era (HR 1.60). These findings suggest that CAS modestly improves access for the shortest candidates, but refinements are needed to address ongoing inequities in this population.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"148 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982511","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":"Backtable Intra-Arterial Administration of C1 Esterase Inhibitor to Deceased Donor Kidney Allografts Improves Post-Transplant Allograft Function: Results of a Randomized Double-Blind Placebo-Controlled Clinical Trial.","authors":"Edmund Huang,Noriko Ammerman,Ashley Vo,Jean Hou,Sanjeev Kumar,Nicole Badash,Ben Falk,Kathleen Hernando,Matthew Gillespie,Irene Kim,Kathlyn Lim,Reiad Najjar,Alice Peng,Bongha Shin,Justin Steggerda,Tsuyoshi Todo,Todd Brennan,Georgios Voidonikolas,Steven Wisel,Peter S Heeger,Stanley C Jordan","doi":"10.1016/j.ajt.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.003","url":null,"abstract":"Ischemia-reperfusion injury (IRI) commonly causes delayed graft function (DGF) after kidney transplantation and is associated with poorer graft function and lower allograft survival. Activation of the lectin complement pathway is one mediator of IRI. In this randomized double-blind placebo-controlled pilot study, we tested whether pre-implantation intragraft administration of C1 esterase inhibitor (C1INH, a lectin/classical pathway inhibitor) into deceased donor organs improves graft function and/or reduces DGF. Forty patients were randomized 1:1 to receive allografts treated with 500 units C1INH or placebo (normal saline) into the transplant renal artery during back-table preparation. We observed no effect on DGF, but recipients of C1INH-treated allografts showed higher eGFR vs. placebo at 6 months (C1INH median: 55 ml/min/1.73 m2, IQR: 42-63; placebo median: 39 ml/min/1.73 m2, IQR 34-50; p=0.02) and 30 months (C1INH median: 54 ml/min/1.73 m2, IQR: 47-66; placebo median: 43 ml/min/1.73 m2, IQR 38-51; p=0.03) without differences in adverse events. Analysis of post-reperfusion biopsies showed positive intra-arterial C1INH staining and reduced C4d staining in C1INH-treated grafts vs controls. Post-transplant serum MBL and classical pathway activity and bradykinin levels did not differ between study arms. We conclude that this treatment strategy improves allograft function independent of DGF, likely via local intragraft complement inhibition. Clinical trial registration number: NCT04696146.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"19 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932839","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":"Graft Biopsy Reimagined: Integrating Morphology and Molecular Maps.","authors":"Umberto Maggiore,Paolo Cravedi","doi":"10.1016/j.ajt.2025.05.005","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.005","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"7 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932838","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":"Molecular diagnosis of kidney allograft rejection based on the Banff Human Organ Transplant (B-HOT) gene panel: a multicenter international study","authors":"Dina Zielinski, Valentin Goutaudier, Marta Sablik, Gillian Divard, Olivier Aubert, Alexis Piedrafita, Fariza Mezine, Jessy Dagobert, Anais Certain, Blaise Robin, Juliette Gueguen, Marion Rabant, Jean-Paul Duong van Huyen, Aurélie Sannier, Christine Randoux-Lebrun, Mehdi Maanaoui, Arnaud Lionet, Jean-Baptiste Gibier, Viviane Gnemmi, Moglie Le Quintrec, Bertrand Chauveau, Agathe Vermorel, Lionel Couzi, Oriol Bestard, Michelle Elias, Kevin Louis, Ivy A. Rosales, R. Neal Smith, Vanderlene L. Kung, Dany Anglicheau, Christophe Legendre, Arnaud Del Bello, Edmund Huang, Benjamin Adam, Nassim Kamar, Robert B. Colvin, Michael Mengel, Carmen Lefaucheur, Alexandre Loupy","doi":"10.1016/j.ajt.2025.04.025","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.04.025","url":null,"abstract":"Transcriptomic analysis of kidney biopsies has demonstrated potential to improve diagnosis of allograft rejection. Here, we developed a molecular assessment of antibody-mediated rejection (AMR) and T-cell-mediated rejection (TCMR) based on the Banff-Human-Organ-Transplant (B-HOT) consensus gene panel. Expression assays of formalin-fixed paraffin-embedded kidney biopsies from well-phenotyped cohorts were used to develop prediction models for AMR and TCMR and an automated report of gene expression-based diagnosis. The study population consisted of 950 kidney allograft biopsies from 10 transplantation centers in Europe and North America. The development cohort included 664 renal allograft biopsies split into a training (n=537) and test set (n=127), and two external validation cohorts (n=286). We performed gene selection using regularized regression and developed several different base models based on B-HOT expression data, which were combined into a single ensemble model for each rejection diagnosis. Model performance was assessed in the test set and the two external validation cohorts, showing good discriminative abilities (respective PR-AUC AMR=0.811, 0.891, 0.832 and TCMR=0.736, 0.810, 0.782). We identified challenging biopsies with histology below diagnostic thresholds for which gene expression-based probability can refine rejection diagnosis. This automated molecular diagnostic system shows potential for improving kidney allograft rejection diagnosis in routine practice and clinical trials.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"27 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930653","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":"Comparable Short-Term Survival in HIV-Positive and HIV-Negative Dual Organ Heart Transplant Recipients: A Call for Increased Access to Organ Donation for People Living with HIV.","authors":"Em Donald,J Batra,Em DeFilippis,J Raikhelkar,D Lotan,Kj Clerkin,G Sayer,N Uriel","doi":"10.1016/j.ajt.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.ajt.2025.05.004","url":null,"abstract":"Access to organ transplantation for HIV-positive individuals is expanding, yet the outcomes of HIV-positive patients requiring multiorgan transplant are not well-defined. Adult individuals in the United Network for Organ Sharing (UNOS) registry who were HIV-positive and received HT between 2010 and 2023 were included. The primary outcome was patient survival. During the study period, 175 HIV-positive patients were transplanted. Twenty-six (14.8%) underwent dual organ transplantation (20 heart/kidney, 4 heart/lung, and 2 heart/liver) at 23 centers. Median age at the time of HT was 56 years (IQR 47-60), majority were male (n=18, 69%), and 46% identified as Black (n= 12). Dilated cardiomyopathy was the most common etiology of heart failure (n=13, 50%). All patients received organs from HIV-negative donors. The probability of surviving at least one year was 87.6% (95% CI 81.0- 92.0) for single-organ recipients and 82.9% for dual organ recipients (95% CI 60.0-93.4). There was no difference in overall survival between HIV-positive and HIV-negative matched controls among dual organ recipients (log-rank p-value = 0.8). Over the last decade, only a small number of HIV-positive individuals with end-stage heart failure have undergone dual organ transplantation with encouraging short-term outcomes.","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"16 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932493","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}