Riley Kahan , Isaac S. Alderete , Qimeng Gao , Benjamin Hughes , Min Zhang , Trevor Gonzalez , Alan Rosales , John Carney , Nihal Aykun , Nader Abraham , Ahmed Hassan , Xiaoyan Nie , Mingqing Song , Kentaro Nakata , Aravind Asokan , Andrew S. Barbas , Matthew G. Hartwig
{"title":"Adeno-associated virus–mediated transduction of PD-L1 in a rodent lung transplant model","authors":"Riley Kahan , Isaac S. Alderete , Qimeng Gao , Benjamin Hughes , Min Zhang , Trevor Gonzalez , Alan Rosales , John Carney , Nihal Aykun , Nader Abraham , Ahmed Hassan , Xiaoyan Nie , Mingqing Song , Kentaro Nakata , Aravind Asokan , Andrew S. Barbas , Matthew G. Hartwig","doi":"10.1016/j.ajt.2025.05.029","DOIUrl":"10.1016/j.ajt.2025.05.029","url":null,"abstract":"<div><div>Acute cellular rejection is a key contributor to chronic lung allograft dysfunction following transplantation; while treatable, traditional immunosuppressive therapies are associated with significant side effects. Gene therapy offers an approach to modulate recipient immune responses while minimizing the toxicity of conventional immunosuppressive therapy. In this study, we evaluated adenoassociated virus (AAV)-mediated programmed death-ligand (PD-L)1 overexpression, an inhibitory ligand of T cells, in a rat single-lung transplant model. Allogeneic Brown Norway lungs were transplanted into Fischer F344 recipients and assigned to 3 groups: (1) AAV9–PD-L1 via the bronchus during static cold storage, (2) no-virus control, or (3) AAV9-luciferase control. All animals received cytotoxic T lymphocyte–associated protein 4 immunoglobulin on postoperative day (POD)1, and killed on POD14. Rejection was evaluated by a blinded lung transplant pathologist, and PD-L1 expression and CD8<sup>+</sup> T cell infiltration assessed via immunohistochemistry. By POD14, the AAV9–PD-L1 group displayed significantly reduced rejection severity (mean score 1.40) compared to controls (mean 3.60; p=0.005). The AAV9-luciferase group exhibited comparable rejection scores to no-virus controls (mean 3.5). Immunohistochemistry confirmed exogenous PD-L1 expression, however no significant difference in CD8+ T cell count was observed between groups. These findings demonstrate that AAV–PD-L1 gene delivery can attenuate acute cellular rejection in lung transplants, offering a potential strategy to improve outcomes.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2082-2089"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191300","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}
Xiaojun Su , Ge Deng , Si Sun , Guangchuan Wang , Samson Hennessy-Strahs , Junhui Li , Mou Wen , Zhuyun Mao , Rafik M. Ghobrial , Xiang Xiao , Wenhao Chen , Xian C. Li
{"title":"Epigenetically modulating macrophage subpopulations to promote long-term allograft survival in a mouse heart transplant model","authors":"Xiaojun Su , Ge Deng , Si Sun , Guangchuan Wang , Samson Hennessy-Strahs , Junhui Li , Mou Wen , Zhuyun Mao , Rafik M. Ghobrial , Xiang Xiao , Wenhao Chen , Xian C. Li","doi":"10.1016/j.ajt.2025.07.2469","DOIUrl":"10.1016/j.ajt.2025.07.2469","url":null,"abstract":"<div><div>Despite much-improved protocols that broadly suppress the adaptive immune cells, most allografts are still lost to chronic rejection, in which macrophages have been prominently featured in the graft. In both clinical and preclinical studies, the graft-infiltrating macrophages often acquire diverse effector activities, especially the M2-biased programs, to mediate graft damage. But the precise mechanisms that regulate such programs remain incompletely defined. In the present study, we took a genome-wide approach to profile the epigenomic changes of M2 polarized macrophages and uncovered bromodomain and extraterminal domain family protein-4 (BRD4) as a critical epigenetic regulator of M2 cells. Further in vitro studies revealed that either blocking BRD4 using a chemical inhibitor or conditional deletion of <em>Brd4</em> in myeloid cells profoundly inhibited the induction of M2 cells. Moreover, in a fully major histocompatibility complex–mismatched heart transplant model, in which treatment with cytotoxic T lymphocyte antigen-4 Ig fusion protein led to the development of chronic rejection, inhibition of BDR4 in transplant recipients resulted in long-term heart allograft survival, which was associated with diminished intragraft M2 cells and absence of histologic features of chronic rejection. Together, our data suggest that macrophages can be epigenetically modified in favor of transplant survival and that BRD4 seems a promising therapeutic target for blocking chronic allograft rejection.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2067-2081"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693238","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":"Increase in New Delhi metallo-β-lactamase–producing carbapenem-resistant Enterobacterales—New York City, 2019-2024","authors":"Marcus R. Pereira","doi":"10.1016/j.ajt.2025.08.001","DOIUrl":"10.1016/j.ajt.2025.08.001","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2036-2037"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144802593","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}
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 , Allan D. Kirk
{"title":"Donor-specific mesenchymal stem cell infusion in human and nonhuman 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 , Allan D. Kirk","doi":"10.1016/j.ajt.2025.05.008","DOIUrl":"10.1016/j.ajt.2025.05.008","url":null,"abstract":"<div><div>We report the results of 2 independent, concurrently performed studies evaluating the safety and efficacy of donor-derived mesenchymal stromal cell<span><span> (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 into 3 groups: control (n = 6), pretransplant thymic irradiation (n = 4), and thymic irradiation with monthly donor-MSC infusion (n = 5). Sirolimus was discontinued at day-180, and </span>belatacept<span><span><span> at day-365 posttransplant. In humans, 6 patients enrolled in ITN062ST underwent transplantation with alemtuzumab induction; 4 received 12 monthly donor-MSC infusions followed by </span>immunosuppression<span> 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 the 5 NHPs that received MSCs rejected while on belatacept </span></span>monotherapy with detectable donor-specific antibodies. Two patients did not initiate ISW due to de novo donor-specific antibodies and borderline rejection, and 2 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.</span></span></div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2114-2126"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","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}
Tzu-Hao Lee , Kara Wegermann , Ken Sutha , George Cholankeril , Chia-Yu Chiu , Nhu Thao Nguyen Galvan , Abbas Rana , John A. Goss , Tyler Lambing , Felice Cinque , Giada Sebastiani , Keyur Patel , Susanna Naggie , Cameron R. Wolfe
{"title":"Beyond the HIV Organ Policy Equity 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 Chiu , 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":"10.1016/j.ajt.2025.05.013","url":null,"abstract":"<div><div>People living with human immunodeficiency virus (HIV) (PWH) face limited access to organ transplantation<span> despite higher rates of end-organ disease. The HIV Organ Policy Equity 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 donors without HIV/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 HIV Organ Policy Equity Act. This manuscript reviewed 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 cultural training, engaging organ procurement organizations and the 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 PWHs receive life-saving transplants.</span></div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2057-2066"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","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}
Murdoch Leeies , David Collister , Julie Ho , Aaron Trachtenberg , Jackie Gruber , Matthew J. Weiss , Jennifer A. Chandler , Owen Mooney , Tricia Carta , Ben Klassen , Chris Draenos , Ken Sutha , Shane Randell , Matthew Strang , Billy Partain , Cameron T. Whitley , Susan Cuvelier , Lauren J. MacKenzie , Sam D. Shemie , Nicole Askin , Carmen Hrymak
{"title":"Corrigendum to “Inequities in organ and tissue donation and transplantation for sexual orientation and gender identity diverse people: A scoping review” [American Journal of Transplantation. Volume 23, Issue 6, June 2023, Pages 707–726]","authors":"Murdoch Leeies , David Collister , Julie Ho , Aaron Trachtenberg , Jackie Gruber , Matthew J. Weiss , Jennifer A. Chandler , Owen Mooney , Tricia Carta , Ben Klassen , Chris Draenos , Ken Sutha , Shane Randell , Matthew Strang , Billy Partain , Cameron T. Whitley , Susan Cuvelier , Lauren J. MacKenzie , Sam D. Shemie , Nicole Askin , Carmen Hrymak","doi":"10.1016/j.ajt.2025.05.017","DOIUrl":"10.1016/j.ajt.2025.05.017","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2265-2266"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547821","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":"Erythropoietin as a macrophage-specific immunoregulatory switch with implications for oncology and transplantation","authors":"Paolo Cravedi, James M. Gardner","doi":"10.1016/j.ajt.2025.08.002","DOIUrl":"10.1016/j.ajt.2025.08.002","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2034-2035"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144805651","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}
Darren E. Stewart , Jessica M. Ruck , Allan B. Massie , Dorry L. Segev , Melissa B. Lesko , Justin C. Chan , Stephanie H. Chang , Travis C. Geraci , Darya Rudym , Mark A. Sonnick , Guido Barmaimon , Luis F. Angel , Jake G. Natalini
{"title":"Graft survival in single versus bilateral lung transplantation for emphysema","authors":"Darren E. Stewart , Jessica M. Ruck , Allan B. Massie , Dorry L. Segev , Melissa B. Lesko , Justin C. Chan , Stephanie H. Chang , Travis C. Geraci , Darya Rudym , Mark A. Sonnick , Guido Barmaimon , Luis F. Angel , Jake G. Natalini","doi":"10.1016/j.ajt.2025.05.025","DOIUrl":"10.1016/j.ajt.2025.05.025","url":null,"abstract":"<div><div><span><span>The benefits of bilateral lung transplantation (BLT) vs single lung transplantation (SLT) are still debated. One impediment to clinical recommendations is that BLT vs SLT advantages may vary based on underlying disease. Because both options are clinically tenable in patients with </span>emphysema<span>, we conducted a comprehensive assessment of lung allograft<span> survival in this population. Using US registry data, we studied time to all-cause allograft failure in 8092 patients 12 years or older, transplanted from 2006 to 2022, adjusting for recipient, donor, and transplant factors by inverse propensity weighting. Median allograft survival was 6.6 years in BLT compared to 5.3 years in SLT, a 25% risk-adjusted survival advantage of </span></span></span><sub>0.8</sub>1.3<sub>1.8</sub><span> years. Risk-adjusted bilateral survival advantages varied between 0.9 and 2.4 years across 11 subgroups. Median allograft survival in BLT was 1.2 years greater than right SLT and 2.0 years greater than left SLT. During the 16-year study period, allograft survival steadily improved for BLT but not for SLT. Although the 25% BLT survival advantage predated the coronavirus 2019 (COVID-19) pandemic, COVID-19 may have contributed to an apparent SLT survival decline. Recognizing the possible influence of residual confounding due to selection biases, these findings may aid offer decision-making when both donor lungs are available.</span></div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2226-2238"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145969","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}
Matthew M. Byrne , Mariana Chávez-Villa , Luis I. Ruffolo , Anthony Loria , Yutaka Endo , Amber Niewiemski , Cristina Jimenez-Soto , Jennifer I. Melaragno , Gopal A. Ramaraju , Priya D. Farooq , Richard F. Dunne , Karen Pineda-Solis , Amit Nair , Mark Orloff , Koji Tomiyama , Roberto Hernandez-Alejandro
{"title":"Corrigendum to ‘The Rochester Protocol for living donor liver transplantation of unresectable colorectal liver metastasis: A 5-year report on selection, approval, and outcomes’ [American Journal of Transplantation 25 (2025) 780–792]","authors":"Matthew M. Byrne , Mariana Chávez-Villa , Luis I. Ruffolo , Anthony Loria , Yutaka Endo , Amber Niewiemski , Cristina Jimenez-Soto , Jennifer I. Melaragno , Gopal A. Ramaraju , Priya D. Farooq , Richard F. Dunne , Karen Pineda-Solis , Amit Nair , Mark Orloff , Koji Tomiyama , Roberto Hernandez-Alejandro","doi":"10.1016/j.ajt.2025.06.023","DOIUrl":"10.1016/j.ajt.2025.06.023","url":null,"abstract":"","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Page 2262"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603893","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}
Isaac S. Alderete , Alexandria L. Soto , Samantha E. Halpern , Arya Pontula , Ewout Muylle , Kentaro Nakata , Kunal J. Patel , Jacob Klapper , Matthew G. Hartwig
{"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 , Ewout Muylle , Kentaro Nakata , Kunal J. Patel , Jacob Klapper , Matthew G. Hartwig","doi":"10.1016/j.ajt.2025.05.011","DOIUrl":"10.1016/j.ajt.2025.05.011","url":null,"abstract":"<div><div><span>Short-statured lung transplant 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 lung transplant candidates listed from 2021 to 2024, categorized into 4 height groups: ≤162 cm, 162 to 170 cm, 170 to 176.5 cm, and >176.5 cm. Competing risk and </span>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 9383 candidates identified, those >176.5 cm had an increased likelihood of transplantation (subdistribution hazard ratio [sHR]: 1.15) compared to the 170 to 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.</div></div>","PeriodicalId":123,"journal":{"name":"American Journal of Transplantation","volume":"25 10","pages":"Pages 2216-2225"},"PeriodicalIF":8.2,"publicationDate":"2025-10-01","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}
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